Effects of Atomoxetine on Brain Activation During Attention & Reading Tasks in Participants With ADHD & Comorbid Dyslexia

Neurophysiology of Attention-Deficit/Hyperactivity Disorder (ADHD) and Comorbid Dyslexia: Functional Magnetic Resonance Imaging (fMRI) Measures of Brain Activation During Attention and Reading Tasks Pre- and Post-Atomoxetine Treatment

This study will evaluate the effects of atomoxetine on brain activation during attention and reading tasks via functional Magnetic Resonance Imaging (fMRI) in participants ages 10 to 16 years old with ADHD and comorbid dyslexia

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder; Dyslexia
• Intervention / Treatment: Drug: Atomoxetine; Drug: Placebo

Detailed Description

This is a randomized, placebo-controlled, double-blind, single site study that uses an fMRI measurement to assess brain activation during attention and reading tasks and the effects of atomoxetine in reducing symptoms of ADHD in participants with ADHD and comorbid dyslexia. Similar assessments are performed in two additional groups of participants with ADHD only and dyslexia only to determine to what extent symptomatic change in the comorbid ADHD & dyslexia is achieved independently by atomoxetine effects on either condition. A healthy control group of non-ADHD, non-dyslexia subjects (20) will be included to monitor practice effects & effects of treatment that may be interpreted as normal maturation. The healthy control group will not be treated with any study medications.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School Of Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants in the ADHD-only or ADHD+dyslexia groups must meet DSM-IV-TR criteria for ADHD
• Participants in the dyslexia-alone group or ADHD+dyslexia groups must meet criteria for dyslexia
• Participants must achieve a score of 80 or more on the Full Scale Intelligence Quotient
• Child or adolescent participants 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 & all related tests
• Participants for healthy control group do not meet DSM-IV-TR criteria for ADHD and/or dyslexia
• Participants for healthy control group must achieve a score of at least 80 but not >120 on the Full Scale Intelligence Quotient

Exclusion Criteria:

• Participants who weigh less than 25.1 kilogram (kg) or greater than 70 kg.
• Participants with severe allergies to more than 1 class of medications or who have had multiple adverse drug reactions
• Participants with prior diagnosis of bipolar I or bipolar II disorder or psychosis
• Participants with documented history of autism, Asperger's syndrome, or pervasive developmental disorder
• Females who are pregnant or breastfeeding
• Participants treated with atomoxetine at a therapeutic dose (1.2 mg/kg/day) for at least 4 to 6 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atomoxetine; Atomoxetine will be administered at 1.0 to 1.4 mg/kg/day given orally once daily in the morning for 16 weeks (study period II). Participants who complete the study period II will be re-randomized in the study period III of 16-week duration to assess maintenance of benefit following discontinuation of treatment with atomoxetine. Participants assigned to atomoxetine during the study period II will be re-randomized to either atomoxetine or placebo whereas participants previously assigned to placebo will receive 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 weeks; Other Names: LY139603
Placebo Comparator: Placebo; Placebo will be packaged in the same way as active comparator to enforce double-blind study design	Drug: Placebo; oral, daily, for 16 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Endpoint in Functional Magnetic Resonance Imaging (fMRI) Activation in Participants With Dyslexia Alone (Pseudoword Rhyming and Semantic-category)	Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) BOLD response (Blood-oxygen-level-dependent response)	Baseline, 16 Weeks
Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Attention Tasks)	Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Attention Tasks)	Baseline, 16 Weeks
Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Pseudoword Rhyming and Semantic-category Tasks)	Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) BOLD response (Blood-oxygen-level-dependent response)	Baseline, 16 Weeks
Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Tasks)	Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Tasks)	Baseline, 16 Weeks
Change From Baseline to Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version (ADHDRS) Total Score in the ADHD or ADHD + Dyslexia	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). Total scores range from 0-54. Higher scores indicate higher impairment and lower scores indicate no impairment. LS mean was calculated using a restricted maximum likelihood (REML)-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	Baseline, 16 weeks
Change From Baseline to Endpoint in Woodcock Johnson Tests of Achievement (WJ III) Word Attack Total Score in Participants With Dyslexia Alone	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores which is a greater range of standard scores. Test 13, Word Attack, measures skill in applying phonic, structural analysis to the pronunciation of unfamiliar printed words. Each individual test scores range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. Least Square (LS) Mean was analyzed using last observation carried forward (LOCF), fixed-effects analysis of covariate (ANCOVA) models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Endpoint in Basic Reading Skills Cluster WJ III in Participants With Dyslexia Alone	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. Basic Reading Skills is an aggregate measure of sight vocabulary, phonics, and structural analysis. It is a combination of Test 1, Letter-Word Identification, which measures the participant's word identification skills, and Test 13, Word Attack, which measures skill in applying phonic and structural analysis skills to the pronunciation of unfamiliar printed words. It is the average (arithmetic mean) of the tests 1 and 13. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 Weeks
Change From Baseline to Endpoint in BADD-A Total Score in Participants With ADHD or ADHD + Dyslexia	The BADD-A is used to assess impairment in executive functions related to ADHD. These include 1) Organizing, prioritizing, and activating to work; 2) Focusing, sustaining and shifting attention to tasks; 3) Regulating alertness, sustaining effort, and processing speed; 4) Managing frustration and modulating emotions; 5) Utilizing working memory and accessing recall (Brown 2001). Scores range from 0-120. The higher the score the more severe the attention-deficit disorder (ADD). 0-39 equate to, "ADD possible but not likely". 40-54 equate to, "ADD probable but not certain". 55-120 equate to, "ADD highly probable". LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	Baseline, 16 Weeks
Change From Baseline to Endpoint in WJ III Individual Test Scores in Participants With Dyslexia Alone	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 Weeks
Change From Baseline to Endpoint in WJ III Individual Test Scores in Participants With ADHD + Dyslexia	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 Weeks
Change From Baseline to Endpoint in WJ III Individual Test Scores in Participants With ADHD Alone	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 Weeks
Change From Baseline to Endpoint in Comprehensive Test of Phonological Processing (CTOPP) Composite Scores in Participants With Dyslexia Alone	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 and lower scores are poor. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 weeks
Change From Baseline to Endpoint in CTOPP Composite Score in Participants With ADHD + Dyslexia	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 and lower scores are poor. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 weeks
Change From Baseline to Endpoint in CTOPP Composite Score in Participants With ADHD Alone	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 and lower scores are poor. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 weeks
Change From Baseline to Endpoint in Gray Oral Reading Tests-4 (GORT-4) in Participants With Dyslexia Alone	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. Lower scores indicate poor reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models of with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 weeks
Change From Baseline to Endpoint in GORT-4 in Participants With ADHD + Dyslexia	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. Lower scores indicate poor reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms of treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 weeks
Change From Baseline to Endpoint in GORT-4 in Participants With ADHD Alone	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. Lower scores indicate poor reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms of treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 weeks
Change From Baseline to Endpoint Test of Word Reading Efficiency (TOWRE) Total Score in Participants With Dyslexia Alone	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. The total standard score ranges from 35-165. Higher scores indicate higher reading proficiency and lower scores indicate lower reading proficiency. LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	Baseline, 16 Weeks
Change From Baseline to Endpoint in TOWRE Total Score in Participants With ADHD or ADHD + Dyslexia	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. The total standard score ranges from 35-165. Higher scores indicate higher reading proficiency and lower scores indicate lower reading proficiency. LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	Baseline, 16 Weeks
Change From Baseline to Endpoint in Working Memory Test Battery for Children (WMTB-C) in Participants With Dyslexia Alone	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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). LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 Weeks
Change From Baseline to Endpoint WMTB-C in Participants With ADHD + Dyslexia	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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). LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 Weeks
Change From Baseline to Endpoint WMTB-C in Participants With ADHD Alone	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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). LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 16 Weeks
Change From Baseline to Endpoint in BADD-A Total Score in Participants With Dyslexia Alone	The BADD-A is used to assess impairment in executive functions related to ADHD. These include 1) Organizing, prioritizing, and activating to work; 2) Focusing, sustaining and shifting attention to tasks; 3) Regulating alertness, sustaining effort, and processing speed; 4) Managing frustration and modulating emotions; 5) Utilizing working memory and accessing recall (Brown 2001). Scores range from 0-120. The higher the score the more severe the ADD. Scores of 0-39 equate to "ADD possible but not likely". Scores of 40-54 equate to "ADD probable but not certain". Scores of 55-120 equate to "ADD highly probable". LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	Baseline, 16 Weeks
Change From Baseline to Endpoint in ADHDRS-IV Total Score in Participants With Dyslexia Alone	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). Total scores range from 0-54. Higher scores indicate higher impairment and lower scores indicate no impairment. LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	Baseline, 16 Weeks
Change From Baseline to Endpoint in WJ III Individual Scores in Participants With Dyslexia Alone	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for gender, baseline score, and age.	Baseline, 32 Weeks
Change From Baseline to Endpoint in WJ III Individual Scores in Participants With ADHD + Dyslexia	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline score, age, and baseline score by treatment interaction.	Baseline, 32 Weeks
Change From Baseline to Endpoint in WJ III Individual Scores in Participants With ADHD Alone	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline score, age, and baseline score by treatment interaction.	Baseline, 32 Weeks
Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With Dyslexia Alone	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 and lower scores are poor. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 32 Weeks
Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With ADHD + Dyslexia	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 and lower scores are poor. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 32 Weeks
Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With ADHD Alone	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 and lower scores are poor. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 32 Weeks
Change From Baseline to Endpoint in GORT-4 in Participants With Dyslexia Alone	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. Lower scores indicate poor reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 32 Weeks
Change From Baseline to Endpoint in GORT-4 in Participants With ADHD + Dyslexia	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. Lower scores indicate poor reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 32 Weeks
Change From Baseline to Endpoint in GORT-4 in Participants With ADHD Alone	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. Lower scores indicate poor reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 32 Weeks
Change From Baseline to Endpoint in Participants in TOWRE Total Score With Dyslexia Alone	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. The total standard score ranges from 35-165. Higher scores indicate higher reading proficiency and lower scores indicate lower reading proficiency. LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	Baseline, 32 Weeks
Change From Baseline to Endpoint in Participants in TOWRE Total Score With ADHD or ADHD + Dyslexia	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. The total standard score ranges from 35-165. Higher scores indicate higher reading proficiency and lower scores indicate lower reading proficiency. LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	Baseline, 32 Weeks
Change From Baseline to Endpoint in Participants in WMTB-C With Dyslexia Alone	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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). LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 32 Weeks
Change From Baseline to Endpoint in Participants in WMTB-C With ADHD + Dyslexia	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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). LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 32 Weeks
Change From Baseline to Endpoint in Participants in WMTB-C With ADHD Alone	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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). LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	Baseline, 32 Weeks
Change From Baseline to Endpoint in BADD-A Total Score in Participants With Dyslexia Alone	The BADD-A is used to assess impairment in executive functions related to ADHD. These include 1) Organizing, prioritizing, and activating to work; 2) Focusing, sustaining and shifting attention to tasks; 3) Regulating alertness, sustaining effort, and processing speed; 4) Managing frustration and modulating emotions; 5) Utilizing working memory and accessing recall (Brown 2001). Scores range from 0-120. The higher the score the more severe the ADD. Scores of 0-39 equate to "ADD possible but not likely". Scores of 40-54 equate to "ADD probable but not certain". Scores of 55-120 equate to "ADD highly probable". LS Mean was calculated using ANCOVA model with terms for gender, baseline score, and age.	Baseline, 32 Weeks
Change From Baseline to Endpoint in BADD-A Total Score in Participants With ADHD or ADHD + Dyslexia	The BADD-A is used to assess impairment in executive functions related to ADHD. These include 1) Organizing, prioritizing, and activating to work; 2) Focusing, sustaining and shifting attention to tasks; 3) Regulating alertness, sustaining effort, and processing speed; 4) Managing frustration and modulating emotions; 5) Utilizing working memory and accessing recall (Brown 2001). Scores range from 0-120. The higher the score the more severe the ADD. Scores of 0-39 equate to "ADD possible but not likely". Scores of 40-54 equate to "ADD probable but not certain". Scores of 55-120 equate to "ADD highly probable". LS Mean was calculated using ANCOVA model with terms for gender, baseline score, and age.	Baseline, 32 Weeks
Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Participants With Dyslexia Alone	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). Total scores range from 0-54. Higher scores indicate higher impairment and lower scores indicate no impairment. LS Mean was calculated using ANCOVA model with terms for gender, baseline score, and age.	Baseline, 32 Weeks
Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Participants With ADHD or ADHD +Dyslexia	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). Total scores range from 0-54. Higher scores indicate higher impairment and lower scores indicate no impairment. LS Mean was calculated using ANCOVA model with terms for gender, baseline score, and age.	Baseline, 32 Weeks
Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Pseudoword Rhyming, Semantic-category)	Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Pseudoword Rhyming, Semantic-category)	From Week 16, Up to Week 32
Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Tasks)	Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Tasks)	From Week 16, Up to 32 Weeks
Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Pseudoword Rhyming and Semantic-category Tasks)	Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Pseudoword Rhyming and Semantic-category Tasks)	From Week 16, Up to Week 32
Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Tasks)	Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Tasks)	From Week 16, Up to Week 32
Change From Baseline to Endpoint in WJ III Individual Scores in Participants With Dyslexia Alone	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline score, age, and baseline score by treatment interaction.	From Week 16, Up to 32 Weeks
Change From Baseline to Endpoint in WJ III Individual Scores in Participants With ADHD + Dyslexia	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline score, age, and baseline score by treatment interaction.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in WJ III Individual Scores in Participants With ADHD Alone	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline score, age, and baseline score by treatment interaction.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With Dyslexia Alone	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 and lower scores are poor. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With ADHD + Dyslexia	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 and lower scores are poor. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With ADHD Alone	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 and lower scores are poor. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	From Week 16, Up to Week 32
Change From Baseline to Endpoint TOWRE Total Score in Participants With Dyslexia Alone	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. The total standard score ranges from 35-165. Higher scores indicate higher reading proficiency and lower scores indicate lower reading proficiency. LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in TOWRE Total Score in Participants With ADHD or ADHD + Dyslexia	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. The total standard score ranges from 35-165. Higher scores indicate higher reading proficiency and lower scores indicate lower reading proficiency. LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in GORT-4 in Participants With Dyslexia Alone	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. Lower scores indicate poor reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in GORT-4 in Participants With ADHD+ Dyslexia	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. Lower scores indicate poor reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in GORT-4 in Participants With ADHD Alone	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. Lower scores indicate poor reading skills. LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in WMTB-C in Participants With Dyslexia Alone	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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). LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	From Week 16, Up to Week 32
Change From Baseline to Endpoint WMTB-C in Participants With ADHD + Dyslexia	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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). LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	From Week 16, Up to Week 32
Change From Baseline to Endpoint WMTB-C in Participants With ADHD Alone	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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). LS mean was analyzed using LOCF, fixed-effects ANCOVA models with terms for treatment, gender, baseline, age, treatment*baseline.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in BADD-A Total Score in Participants With Dyslexia Alone	The BADD-A is used to assess impairment in executive functions related to ADHD. These include 1) Organizing, prioritizing, and activating to work; 2) Focusing, sustaining and shifting attention to tasks; 3) Regulating alertness, sustaining effort, and processing speed; 4) Managing frustration and modulating emotions; 5) Utilizing working memory and accessing recall (Brown 2001). Scores range from 0-120. The higher the score the more severe the ADD. Scores of 0-39 equate to "ADD possible but not likely". Scores of 40-54 equate to "ADD probable but not certain". Scores of 55-120 equate to "ADD highly probable". LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in BADD-A Total Score in Participants With ADHD or ADHD + Dyslexia	The BADD-A is used to assess impairment in executive functions related to ADHD. These include 1) Organizing, prioritizing, and activating to work; 2) Focusing, sustaining and shifting attention to tasks; 3) Regulating alertness, sustaining effort, and processing speed; 4) Managing frustration and modulating emotions; 5) Utilizing working memory and accessing recall (Brown 2001). Scores range from 0-120. The higher the score the more severe the ADD. Scores of 0-39 equate to "ADD possible but not likely". Scores of 40-54 equate to "ADD probable but not certain". Scores of 55-120 equate to "ADD highly probable". LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in ADHDRS-IV Total Score in Participants With Dyslexia Alone	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). Total scores range from 0-54. Higher scores indicate higher impairment and lower scores indicate no impairment. LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	From Week 16, Up to Week 32
Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Participants With ADHD or ADHD + Dyslexia	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). Total scores range from 0-54. Higher scores indicate higher impairment and lower scores indicate no impairment. LS mean was calculated using a REML-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.	From Week 16, Up to Week 32
The Number of Participants With Treatment Emergent Adverse Events (TEAE) in Participants With Dyslexia	The number of participants who experienced one or more treatment emergent adverse events (TEAEs) and who had Dyslexia A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.	16 Weeks
The Number of Participants With TEAE in Participants With ADHD or ADHD+Dyslexia.	The number of participants who experienced one or more TEAEs and who had ADHD and ADHD+Dyslexia. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.	16 Weeks
The Number of Participants With TEAE in Participants With Dyslexia	The number of participants with at least one TEAE and had Dyslexia. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.	From 16 Weeks Up to Week 32
The Number of Participants With TEAE in Participants With ADHD or ADHD+Dyslexia.	The number of participants who experienced one or more TEAEs with ADHD and ADHD + Dyslexia. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.	From Week 16 Up to Week 32
Number of Participants With Adverse Events	Number of participants who had at least one adverse event. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.	32 Weeks
Change From Baseline to Endpoint in WJ III Individual Scores in Healthy Participants	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills.	Baseline, 16 Weeks
Change From Baseline to Endpoint in CTOPP Composite Scores in Healthy Participants	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 and lower scores are poor.	Baseline, 16 Weeks
Change From Baseline to Endpoint in GORT-4 in Healthy Participants	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. Lower scores indicate poor reading skills.	Baseline, 16 weeks
Change From Baseline to Endpoint TOWRE Total Score in Healthy Participants	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. The total standard score ranges from 35-165. Higher scores indicate higher reading proficiency and lower scores indicate lower reading proficiency. LS mean was calculated using a REML-based, MMRM analyses which includes diagnostic group, visit, and diagnostic group-by-visit interaction.	Baseline, 16 Weeks
Change From Baseline to Endpoint in WMTB-C in Healthy Participants	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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 to Endpoint in BADD-A Total Score in Healthy Participants	The BADD-A is used to assess impairment in executive functions related to ADHD. These include 1) Organizing, prioritizing, and activating to work; 2) Focusing, sustaining and shifting attention to tasks; 3) Regulating alertness, sustaining effort, and processing speed; 4) Managing frustration and modulating emotions; 5) Utilizing working memory and accessing recall (Brown 2001). Scores range from 0-120. The higher the score the more severe the ADD. Scores of 0-39 equate to "ADD possible but not likely". Scores of 40-54 equate to "ADD probable but not certain". Scores of 55-120 equate to "ADD highly probable". LS mean was calculated using a REML-based, MMRM analysis which includes the effects of diagnostic group, visit, and diagnostic group-by-visit interaction.	Baseline, 16 Weeks
Change From Baseline to Endpoint in ADHDRS-IV Total Score in Healthy Participants	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). Total scores range from 0-54. Higher scores indicate higher impairment and lower scores indicate no impairment. LS mean was calculated using a REML-based, MMRM analysis which includes diagnostic group, visit, and diagnostic group-by-visit interaction.	Baseline, 16 Weeks
Change From Baseline to Endpoint in WJ III Individual Scores in Healthy Participants	WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores, which is a greater range of standard scores. Scores for each individual test range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills.	Baseline, 32 Weeks
Change From Baseline to Endpoint in CTOPP Composite Scores in Healthy Participants	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 and lower scores are poor.	Baseline, 32 weeks
Change From Baseline to Endpoint in GORT-4 in Healthy Participants	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. Lower scores indicate poor reading skills.	Baseline, 32 Weeks
Change From Baseline to Endpoint in TOWRE Total Score in Healthy Participants	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. The total standard score ranges from 35-165. Higher scores indicate higher reading proficiency and lower scores indicate lower reading proficiency. LS mean was calculated using a REML-based, MMRM analysis which includes diagnostic group, visit, and diagnostic group-by-visit interaction.	Baseline, 32 Weeks
Change From Baseline to Endpoint in WMTB-C in Healthy Participants	WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better, Lower scores are poor) 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 to Endpoint in BADD-A Total Score in Healthy Participants	The BADD-A is used to assess impairment in executive functions related to ADHD. These include 1) Organizing, prioritizing, and activating to work; 2) Focusing, sustaining and shifting attention to tasks; 3) Regulating alertness, sustaining effort, and processing speed; 4) Managing frustration and modulating emotions; 5) Utilizing working memory and accessing recall (Brown 2001). Scores range from 0-120. The higher the score the more severe the ADD. Scores of 0-39 equate to "ADD possible but not likely". Scores of 40-54 equate to "ADD probable but not certain". Scores of 55-120 equate to "ADD highly probable". LS mean was calculated using a REML-based, MMRM which includes the effects of diagnostic group, visit, diagnostic group-by-visit interaction.	Baseline, 32 Weeks
Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Healthy Participants	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). Total scores range from 0-54. Higher scores indicate higher impairment and lower scores indicate no impairment. LS mean was calculated using a REML-based, MMRM analysis which includes the effects of diagnostic group, visit, diagnostic group-by-visit interaction.	Baseline, 32 Weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: July 14, 2008
• First Submitted That Met QC Criteria: July 14, 2008
• First Posted (Estimate): July 16, 2008

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: October 9, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Language Disorders; Communication Disorders; Learning Disabilities; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Dyslexia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride
• Other Study ID Numbers: 12212 (Other Identifier: Company Internal); B4Z-US-LYEI (Other Identifier: Eli Lilly and Company); 2019-000419-98 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)