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

Time frame: Baseline, 16 weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline ADHDRS-IV-Parent: Inv measurements.

Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) BOLD response (Blood-oxygen-level-dependent response)

Time frame: Baseline, 16 Weeks

Population: All participants who received study drug, had ADHD or ADHD + Dyslexia and had fMRI data.

Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Tasks)

Time frame: Baseline, 16 Weeks

Population: Stroop Tasks data were not collected.

Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Attention Tasks)

Time frame: Baseline, 16 Weeks

Population: Stroop Tasks data were not collected.

Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) BOLD response (Blood-oxygen-level-dependent response)

Time frame: Baseline, 16 Weeks

Population: All participants who received study drug, had Dyslexia Alone and had fMRI data.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline WJ III measurements.

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.

Time frame: Baseline, 32 Weeks

Population: All healthy participants who had evaluable baseline and post baseline ADHDRS-IV measurements.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline ADHDRS-IV-Parent: Inv measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: From Week 16, Up to Week 32

Population: All randomized participants who received at least one dose of study drug and had baseline and post baseline ADHDRS-IV measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline ADHDRS-IV-Parent: Inv measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: Baseline, 16 Weeks

Population: All healthy participants who had evaluable baseline and post baseline ADHDRS-IV measurements.

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.

Time frame: From Week 16, Up to Week 32

Population: All randomized participants who received at least one dose of study drug and had baseline and post baseline ADHDRS-IV measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline ADHDRS-IV-Parent: Inv measurements.

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.

Time frame: Baseline, 32 Weeks

Population: All healthy participants who had evaluable baseline and post baseline BADD-A measurements.

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.

Time frame: Baseline, 16 Weeks

Population: All participants who had evaluable baseline and post baseline BADD-A measurements.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline BADD-A measurements.

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.

Time frame: From Week 16, Up to Week 32

Population: All randomized participants who received at least one dose of study drug and had baseline and post baseline BADD-A measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline BADD-A measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline BADD-A measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: From Week 16, Up to Week 32

Population: All randomized participants who received at least one dose of study drug and had baseline and post baseline BADD-A measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline BADD-A measurements.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline WJ III measurements.

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.

Time frame: Baseline, 16 weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline CTOPP measurements.

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.

Time frame: Baseline, 16 weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline CTOPP measurements.

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.

Time frame: Baseline, 16 weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline CTOPP measurements.

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.

Time frame: Baseline, 16 Weeks

Population: All healthy participants who had evaluable baseline and post baseline CTOPP measurements.

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.

Time frame: Baseline, 32 weeks

Population: All healthy participants who had evaluable baseline and post baseline CTOPP measurements.

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.

Time frame: From Week 16, Up to Week 32

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline CTOPP measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline CTOPP measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline CTOPP measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: From Week 16, Up to Week 32

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline CTOPP measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline CTOPP measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: From Week 16, Up to Week 32

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline CTOPP measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Pseudoword Rhyming and Semantic-category Tasks)

Time frame: From Week 16, Up to Week 32

Population: For this outcome measure, there were no data collected beyond 16 weeks.

Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Tasks)

Time frame: From Week 16, Up to Week 32

Population: Stroop Tasks data were not collected.

Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Pseudoword Rhyming, Semantic-category)

Time frame: From Week 16, Up to Week 32

Population: For this outcome measure, there were no data collected beyond 16 weeks.

Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Tasks)

Time frame: From Week 16, Up to 32 Weeks

Population: Stroop Tasks data were not collected.

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.

Time frame: Baseline, 16 weeks

Population: All healthy participants who had evaluable baseline and post baseline GORT-4 measurements.

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.

Time frame: Baseline, 32 Weeks

Population: All healthy participants who had evaluable baseline and post baseline GORT-4 measurements.

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.

Time frame: Baseline, 16 weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline GORT-4 measurements.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline GORT-4 measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: From Week 16, Up to Week 32

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline GORT-4 measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 16 weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline GORT-4 measurements.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline GORT-4 measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: From Week 16, Up to Week 32

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline GORT-4 measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline GORT-4 measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: From Week 16, Up to Week 32

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline GORT-4 measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 16 weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline GORT-4 measurements.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline TOWRE measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline TOWRE measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who had received atomoxetine in both phases and had evaluable baseline and post baseline WTMB-C measurements.No participants by design were on placebo for both study periods II and III.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who had received atomoxetine in both phases and had evaluable baseline and post baseline WTMB-C measurements.No participants by design were on placebo for both study periods II and III.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline WMTB-C measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: Baseline, 32 Weeks

Population: All healthy participants who had evaluable baseline and post baseline TOWRE measurements.

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.

Time frame: From Week 16, Up to Week 32

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline TOWRE measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline TOWRE measurements.

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.

Time frame: Baseline, 16 Weeks

Population: All healthy participants who had evaluable baseline and post baseline WJ III measurements.

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.

Time frame: Baseline, 32 Weeks

Population: All healthy participants who had baseline and post-baseline WJ III measurements.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline WJ III measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: From Week 16, Up to Week 32

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline WJ III measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: From Week 16, Up to Week 32

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline WJ III measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline WJ III measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: From Week 16, Up to 32 Weeks

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline WJ III measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 32 Weeks

Population: All randomized participants who received atomoxetine in both phases and had evaluable baseline and post baseline WJ III measurements. No participants by design were on placebo for both study periods II and III.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who had a baseline and post-baseline WJ III measurement.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who had a baseline and post-baseline WJ III measurement.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who had a WJ III baseline and post-baseline measurement.

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).

Time frame: Baseline, 32 Weeks

Population: All healthy participants who had evaluable baseline and post baseline WMTB-C measurements.

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).

Time frame: Baseline, 16 Weeks

Population: All healthy participants who had evaluable baseline and post baseline WMTB-C measurements.

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.

Time frame: From Week 16, Up to Week 32

Population: All randomized participants who received at least one dose of study drug and had baseline and post baseline WMTB-C measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline WMTB-C measurements.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline TOWRE measurements.

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.

Time frame: Baseline, 16 Weeks

Population: All healthy participants who had evaluable baseline and post baseline TOWRE measurements.

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.

Time frame: From Week 16, Up to Week 32

Population: All participants who received at least one dose of study drug and had evaluable baseline and post baseline TOWRE measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline WMTB-C measurements.

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.

Time frame: From Week 16, Up to Week 32

Population: All randomized participants who received at least one dose of study drug and had baseline and post baseline WMTB-C measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: Baseline, 16 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline WMTB-C measurements.

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.

Time frame: From Week 16, Up to Week 32

Population: All randomized participants who received at least one dose of study drug and had baseline and post baseline WMTB-C measurements. The objectives for this portion of the trial centered around participants already exposed to ATX for 16 weeks and therefore no data for PLA/ATX are given.

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.

Time frame: 32 Weeks

Population: All randomized participants who received at least one dose of study drug.

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.

Time frame: 16 Weeks

Population: All randomized participants who received at least one dose of study drug.

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.

Time frame: From Week 16 Up to Week 32

Population: All randomized participants who received at least one dose of study drug.

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.

Time frame: From 16 Weeks Up to Week 32

Population: All randomized participants who received at least one dose of study drug.

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.

Time frame: 16 Weeks

Population: All randomized participants who received at least one dose of study drug.