Attention Deficit Hyperactivity Disorder, Reading Disorder
Conditions
Brief summary
To test the hypothesis that a 4 week treatment with atomoxetine is more effective than placebo in patients with combined type Attention Deficit/Hyperactivity Disorder (ADHD), patients with only Reading Disorder, and patients with combined type ADHD and Reading Disorder.
Interventions
DRUGAtomoxetine Hydrochloride
Atomoxetine, 1.2 mg/kg/day, by mouth (PO)
DRUGplacebo
Placebo, every day (QD), by mouth (PO)
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 12 Years
Healthy volunteers
Yes
Inclusion criteria
* Clinical diagnosis with Attention Deficit Hyperactivity Disorder and/or Reading Disorder
Exclusion criteria
* Patients with Conduct Disorder * Patients who have a history of Bipolar I or II Disorder, psychosis, or Pervasive Development Disorder. * Patients who have a current diagnosis of Vocal Tic Disorder, Obsessive Compulsive Disorder, Major Depressive Disorder, Post Traumatic Stress Disorder, Anxiety Disorder, and certain other learning disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset | Baseline and 4 weeks of therapy | SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal. |
| Lexical Decision Task Mean Reaction Time: Correct Words | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | Measure of reaction time to identify whether a word displayed on a computer is a real or correct word versus a pseudo word. During the performance of the lexical decision task that was presented on a computer, the reaction times and accuracy of responses were measured. Data presented are the mean reaction times over the 4 weeks of each therapy for identifying correct words correctly. |
| Lexical Decision Task Mean Reaction Time: Pseudo Words | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | Measure of reaction time to identify whether a word displayed on a computer is a pseudo word versus a real or correct word. During the performance of the lexical decision task that was presented on a computer, the reaction times and accuracy of responses were measured. Data presented are the mean reaction times over the 4 weeks of each therapy for identifying pseudo words correctly. |
| Working Memory by Corsi Block Tapping Test (CBTT) | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | Measures the visuo-spatial working memory span, and corresponds to the longest sequence of blocks that has been reproduced correctly at least once. Scores can range from 3 to 8, with the higher score indicating better function. |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total Score | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total score is the sum of the scores on the 18 items and range from 0 to 54. |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Inattention Subscale | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | Measures the degree of inattention symptoms based on answers to 9 items. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often), for a total Inattention Subscale score range of 0 to 27. |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Hyperactivity-Impulsivity Subscale | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | Measures the degree of hyperactivity-impulsivity symptoms, based on answers to 9 items. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often) for a total Hyperactivity-Impulsivity Subscale score of 0 to 27. |
| Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset | Baseline and 4 weeks of therapy | SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal. |
| Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale | 4 week therapy endpoint | Measures total improvement (or worsening) of a patient's ADHD symptoms from the beginning of treatment (1=very much improved, 7=very much worsened). |
| Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale | 4 week therapy endpoint | Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients). |
| Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudohomophones | Baseline and 4 weeks of therapy | Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudohomophones and pseudo words. Data presented here are for reaction time to identifying psuedohomophones correctly. |
| Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudo Words | Baseline and 4 weeks of therapy | Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to identifying pseudo words correctly. |
| Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudohomophones | Baseline and 4 weeks of therapy | Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to identifying psuedohomophones correctly. |
| Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudo Words | Baseline and 4 weeks of therapy | Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to indentifying pseudo words correctly. |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total T-Score | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total score is computed as the sum of the scores on each of the 18 items. Total score is the sum of the scores on the 18 items and range from 0 to 54. Total T-score = (Total Score - 50)/10. Total T-score ranges from -5 (low severity) to 0.4 (high severity). |
Countries
Belgium, Netherlands
Participant flow
Pre-assignment details
Period I: screening/washout (89 patients screened, 13 screen-failures;45 controls screened). Period II (Visits 2-5): patients received treatment for 4 weeks and then underwent 2-week washout period after which they crossed over to receive the alternate treatment for 4 additional weeks. Period III (Visits 6-12): optional open-label (1 country only).
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine First, Then Placebo Atomoxetine 1.2 mg/kg/day for 4 weeks, 2 week washout, and then placebo for 4 weeks | 39 |
| Placebo First, Then Atomoxetine Placebo for 4 weeks, 2 week washout, and then atomoxetine 1.2 mg/kg/day for 4 weeks. | 37 |
| Normal Control Untreated normal controls were children selected from the general population. The normal control was matched (have same proportion) by sex (male/female) and by age (have same age range) as the study population. | 27 |
| Reading Disordered Control Untreated reading disordered control group was comprised of children with reading disorder who received standard remedial teaching therapy. | 18 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Study Period II | Adverse Event | 0 | 1 | 0 | 0 |
| Study Period II | Entry Criteria Exclusion | 0 | 0 | 1 | 0 |
| Study Period II | Parent/Caregiver Decision | 0 | 1 | 0 | 0 |
| Study Period II | Withdrawal by Subject | 0 | 3 | 0 | 0 |
| Study Period III | Adverse Event | 1 | 0 | 0 | 0 |
| Study Period III | Lack of Efficacy | 3 | 3 | 0 | 0 |
| Study Period III | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Study Period III | Parent/Caregiver Decision | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Atomoxetine First, Then Placebo | Placebo First, Then Atomoxetine | Normal Control | Reading Disordered Control | Total |
|---|---|---|---|---|---|
| Age Continuous | 10.0 years STANDARD_DEVIATION 1.34 | 9.9 years STANDARD_DEVIATION 1.25 | 9.9 years STANDARD_DEVIATION 1.01 | 10.6 years STANDARD_DEVIATION 0.99 | 10.0 years STANDARD_DEVIATION 1.2 |
| Region of Enrollment Belgium | 18 participants | 15 participants | 0 participants | 16 participants | 49 participants |
| Region of Enrollment Netherlands | 21 participants | 22 participants | 27 participants | 2 participants | 72 participants |
| Sex: Female, Male Female | 13 Participants | 10 Participants | 10 Participants | 5 Participants | 38 Participants |
| Sex: Female, Male Male | 26 Participants | 27 Participants | 17 Participants | 13 Participants | 83 Participants |
| Study Arm - Diagnosis ADHD-Combined Type | 13 participants | 15 participants | 0 participants | 0 participants | 28 participants |
| Study Arm - Diagnosis ADHD-Combined Type + Reading Disorder | 15 participants | 10 participants | 0 participants | 0 participants | 25 participants |
| Study Arm - Diagnosis No Disorder | 0 participants | 0 participants | 27 participants | 0 participants | 27 participants |
| Study Arm - Diagnosis Reading Disorder | 11 participants | 12 participants | 0 participants | 18 participants | 41 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 76 | 35 / 74 | 24 / 25 |
| serious Total, serious adverse events | 0 / 76 | 0 / 74 | 0 / 25 |
Outcome results
Primary
Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm
SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal.
Time frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm | ADHD-Combined Type | 299.90 milliseconds (msec) | Standard Error 13.29 |
| Atomoxetine | Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm | Reading Disorder | 265.61 milliseconds (msec) | Standard Error 14.24 |
| Atomoxetine | Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm | ADHD-C + Reading Disorder | 277.38 milliseconds (msec) | Standard Error 13.8 |
| Atomoxetine | Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm | Overall | 280.97 milliseconds (msec) | Standard Error 7.96 |
| Placebo | Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm | Overall | 287.29 milliseconds (msec) | Standard Error 8.84 |
| Placebo | Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm | ADHD-Combined Type | 308.82 milliseconds (msec) | Standard Error 14.53 |
| Placebo | Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm | ADHD-C + Reading Disorder | 292.53 milliseconds (msec) | Standard Error 15.46 |
| Placebo | Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm | Reading Disorder | 260.51 milliseconds (msec) | Standard Error 16.02 |
Comparison: Least Squares Mean (LSMean) values were calculated from the measurements taken at baseline and at the end of each 4 week therapy period.p-value: 0.504Repeated Measures
Secondary
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Hyperactivity-Impulsivity Subscale
Measures the degree of hyperactivity-impulsivity symptoms, based on answers to 9 items. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often) for a total Hyperactivity-Impulsivity Subscale score of 0 to 27.
Time frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Hyperactivity-Impulsivity Subscale | ADHD-Combined Type | 15.51 units on a scale | Standard Error 1.14 |
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Hyperactivity-Impulsivity Subscale | ADHD-Combined Type + Reading Disorder | 10.32 units on a scale | Standard Error 1.27 |
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Hyperactivity-Impulsivity Subscale | Overall | 12.91 units on a scale | Standard Error 0.85 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Hyperactivity-Impulsivity Subscale | ADHD-Combined Type | 17.24 units on a scale | Standard Error 0.96 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Hyperactivity-Impulsivity Subscale | ADHD-Combined Type + Reading Disorder | 17.03 units on a scale | Standard Error 1.12 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Hyperactivity-Impulsivity Subscale | Overall | 17.13 units on a scale | Standard Error 0.73 |
Comparison: Least Squares Mean (LSMean) values were calculated from the measurements taken at baseline and at the end of each 4 week therapy period.p-value: <0.001Repeated Measures
Secondary
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Inattention Subscale
Measures the degree of inattention symptoms based on answers to 9 items. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often), for a total Inattention Subscale score range of 0 to 27.
Time frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Inattention Subscale | ADHD-Combined Type | 15.27 units on a scale | Standard Error 1.09 |
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Inattention Subscale | ADHD-Combined Type + Reading Disorder | 12.25 units on a scale | Standard Error 1.22 |
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Inattention Subscale | Overall | 13.76 units on a scale | Standard Error 0.82 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Inattention Subscale | ADHD-Combined Type | 17.82 units on a scale | Standard Error 0.93 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Inattention Subscale | ADHD-Combined Type + Reading Disorder | 18.28 units on a scale | Standard Error 1.09 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Inattention Subscale | Overall | 18.05 units on a scale | Standard Error 0.7 |
Comparison: Least Squares Mean (LSMean) values were calculated from the measurements taken at baseline and at the end of each 4 week therapy period.p-value: <0.001Repeated Measures
Secondary
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total Score
Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total score is the sum of the scores on the 18 items and range from 0 to 54.
Time frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total Score | ADHD-Combined Type | 30.86 units on a scale | Standard Error 2.14 |
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total Score | ADHD-Combined Type + Reading Disorder | 22.44 units on a scale | Standard Error 2.38 |
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total Score | Overall | 26.65 units on a scale | Standard Error 1.6 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total Score | ADHD-Combined Type | 35.20 units on a scale | Standard Error 1.78 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total Score | ADHD-Combined Type + Reading Disorder | 35.17 units on a scale | Standard Error 2.07 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total Score | Overall | 35.18 units on a scale | Standard Error 1.34 |
Comparison: Least Squares Mean (LSMean) values were calculated from the measurements taken at baseline and at the end of each 4 week therapy period.p-value: <0.001Repeated Measures
Secondary
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total T-Score
Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total score is computed as the sum of the scores on each of the 18 items. Total score is the sum of the scores on the 18 items and range from 0 to 54. Total T-score = (Total Score - 50)/10. Total T-score ranges from -5 (low severity) to 0.4 (high severity).
Time frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total T-Score | ADHD-Combined Type | -1.91 T-Score of units on a scale | Standard Error 0.21 |
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total T-Score | ADHD-Combined Type + Reading Disorder | -2.76 T-Score of units on a scale | Standard Error 0.24 |
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total T-Score | Overall | -2.34 T-Score of units on a scale | Standard Error 0.16 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total T-Score | ADHD-Combined Type | -1.48 T-Score of units on a scale | Standard Error 0.18 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total T-Score | ADHD-Combined Type + Reading Disorder | -1.48 T-Score of units on a scale | Standard Error 0.21 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total T-Score | Overall | -1.48 T-Score of units on a scale | Standard Error 0.13 |
Comparison: Least Squares Mean (LSMean) values were calculated from the measurements taken at baseline and at the end of each 4 week therapy period.p-value: <0.001Repeated Measures
Secondary
Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset
SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal.
Time frame: Baseline and 4 weeks of therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset | -0.25 milliseconds | Standard Deviation 53.41 |
| Placebo | Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset | -34.0 milliseconds | Standard Deviation 33.91 |
| Reading Disordered Control | Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset | 0.05 milliseconds | Standard Deviation 24.08 |
Comparison: ANCOVA model with baseline value, study arm as covariates for ADHD-C+RD versus RD controls.p-value: 0.579ANCOVA
Comparison: ANCOVA model with baseline value, study arm as covariates for RD versus RD controls.p-value: 0.144ANCOVA
Secondary
Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset
SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal.
Time frame: Baseline and 4 weeks of therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset | 7.95 milliseconds | Standard Deviation 48.21 |
| Placebo | Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset | 11.22 milliseconds | Standard Deviation 62.77 |
Comparison: ANCOVA model with baseline value, study arm as covariates for ADHD-C versus Normal controls.p-value: 0.97ANCOVA
Secondary
Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudohomophones
Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to identifying psuedohomophones correctly.
Time frame: Baseline and 4 weeks of therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudohomophones | -170.81 milliseconds | Standard Deviation 243.33 |
| Placebo | Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudohomophones | -241.00 milliseconds | Standard Deviation 317.47 |
| Reading Disordered Control | Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudohomophones | -254.86 milliseconds | Standard Deviation 266.46 |
Comparison: ANCOVA model with baseline value, study arm as covariates for ADHD-C+RD versus RD controls.p-value: 0.302ANCOVA
Comparison: ANCOVA model with baseline value, study arm as covariate for RD versus RD controls.p-value: 0.663ANCOVA
Secondary
Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudo Words
Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to indentifying pseudo words correctly.
Time frame: Baseline and 4 weeks of therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudo Words | -113.06 milliseconds | Standard Deviation 432.68 |
| Placebo | Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudo Words | -213.00 milliseconds | Standard Deviation 512.33 |
| Reading Disordered Control | Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudo Words | -368.14 milliseconds | Standard Deviation 422.42 |
Comparison: ANCOVA model with baseline value, study arm as covariate for ADHD-C+RD versus RD controls.p-value: 0.07ANCOVA
Comparison: ANCOVA model with baseline value, study arm as covariate for RD versus RD controls.p-value: 0.179ANCOVA
Secondary
Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudohomophones
Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudohomophones and pseudo words. Data presented here are for reaction time to identifying psuedohomophones correctly.
Time frame: Baseline and 4 weeks of therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudohomophones | -230.40 milliseconds | Standard Deviation 239.43 |
| Placebo | Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudohomophones | -339.17 milliseconds | Standard Deviation 176.32 |
Comparison: ANCOVA model with baseline value, study arm as covariates for ADHD-C versus normal controls.p-value: 0.508ANCOVA
Secondary
Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudo Words
Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to identifying pseudo words correctly.
Time frame: Baseline and 4 weeks of therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudo Words | -523.20 milliseconds | Standard Deviation 524.36 |
| Placebo | Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudo Words | -536.00 milliseconds | Standard Deviation 303.27 |
Comparison: ANCOVA model with baseline value, study arm as covariate for ADHD-C versus normal controlsp-value: 0.769ANCOVA
Secondary
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale
Measures total improvement (or worsening) of a patient's ADHD symptoms from the beginning of treatment (1=very much improved, 7=very much worsened).
Time frame: 4 week therapy endpoint
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale | ADHD-Combined Type | 3.69 units on a scale | Standard Error 0.24 |
| Atomoxetine | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale | ADHD-Combined Type + Reading Disorder | 2.98 units on a scale | Standard Error 0.24 |
| Atomoxetine | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale | Overall | 3.34 units on a scale | Standard Error 0.17 |
| Placebo | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale | ADHD-Combined Type | 3.70 units on a scale | Standard Error 0.23 |
| Placebo | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale | ADHD-Combined Type + Reading Disorder | 3.76 units on a scale | Standard Error 0.24 |
| Placebo | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale | Overall | 3.73 units on a scale | Standard Error 0.16 |
p-value: 0.094Repeated Measures
Secondary
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale
Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).
Time frame: 4 week therapy endpoint
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale | ADHD-Combined Type | 4.05 units on a scale | Standard Error 0.21 |
| Atomoxetine | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale | ADHD-Combined Type + Reading Disorder | 3.65 units on a scale | Standard Error 0.21 |
| Atomoxetine | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale | Overall | 3.85 units on a scale | Standard Error 0.14 |
| Placebo | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale | ADHD-Combined Type | 3.73 units on a scale | Standard Error 0.19 |
| Placebo | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale | ADHD-Combined Type + Reading Disorder | 4.34 units on a scale | Standard Error 0.2 |
| Placebo | Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale | Overall | 4.04 units on a scale | Standard Error 0.13 |
p-value: 0.312Repeated Measures
Secondary
Lexical Decision Task Mean Reaction Time: Correct Words
Measure of reaction time to identify whether a word displayed on a computer is a real or correct word versus a pseudo word. During the performance of the lexical decision task that was presented on a computer, the reaction times and accuracy of responses were measured. Data presented are the mean reaction times over the 4 weeks of each therapy for identifying correct words correctly.
Time frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Lexical Decision Task Mean Reaction Time: Correct Words | ADHD-Combined Type | 1182.9 milliseconds | Standard Error 50.23 |
| Atomoxetine | Lexical Decision Task Mean Reaction Time: Correct Words | Reading Disorder | 1172.4 milliseconds | Standard Error 51.75 |
| Atomoxetine | Lexical Decision Task Mean Reaction Time: Correct Words | ADHD-C + Reading Disorder | 1201.9 milliseconds | Standard Error 51.22 |
| Atomoxetine | Lexical Decision Task Mean Reaction Time: Correct Words | Overall | 1185.7 milliseconds | Standard Error 29.49 |
| Placebo | Lexical Decision Task Mean Reaction Time: Correct Words | Overall | 1265.5 milliseconds | Standard Error 22.61 |
| Placebo | Lexical Decision Task Mean Reaction Time: Correct Words | ADHD-Combined Type | 1291.9 milliseconds | Standard Error 38.13 |
| Placebo | Lexical Decision Task Mean Reaction Time: Correct Words | ADHD-C + Reading Disorder | 1305.9 milliseconds | Standard Error 39.43 |
| Placebo | Lexical Decision Task Mean Reaction Time: Correct Words | Reading Disorder | 1198.6 milliseconds | Standard Error 40.24 |
Comparison: Least Squares Mean (LSMean) values were calculated from the measurements taken at baseline and at the end of each 4 week therapy period.p-value: 0.005Repeated Measures
Secondary
Lexical Decision Task Mean Reaction Time: Pseudo Words
Measure of reaction time to identify whether a word displayed on a computer is a pseudo word versus a real or correct word. During the performance of the lexical decision task that was presented on a computer, the reaction times and accuracy of responses were measured. Data presented are the mean reaction times over the 4 weeks of each therapy for identifying pseudo words correctly.
Time frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Lexical Decision Task Mean Reaction Time: Pseudo Words | ADHD-Combined Type | 1403.0 milliseconds | Standard Error 63.72 |
| Atomoxetine | Lexical Decision Task Mean Reaction Time: Pseudo Words | Reading Disorder | 1365.0 milliseconds | Standard Error 65.62 |
| Atomoxetine | Lexical Decision Task Mean Reaction Time: Pseudo Words | ADHD-C + Reading Disorder | 1426.1 milliseconds | Standard Error 64.83 |
| Atomoxetine | Lexical Decision Task Mean Reaction Time: Pseudo Words | Overall | 1398.0 milliseconds | Standard Error 37.33 |
| Placebo | Lexical Decision Task Mean Reaction Time: Pseudo Words | Overall | 1458.2 milliseconds | Standard Error 29.63 |
| Placebo | Lexical Decision Task Mean Reaction Time: Pseudo Words | ADHD-Combined Type | 1475.4 milliseconds | Standard Error 50.08 |
| Placebo | Lexical Decision Task Mean Reaction Time: Pseudo Words | ADHD-C + Reading Disorder | 1487.0 milliseconds | Standard Error 51.73 |
| Placebo | Lexical Decision Task Mean Reaction Time: Pseudo Words | Reading Disorder | 1412.2 milliseconds | Standard Error 52.9 |
Comparison: Least Squares Mean (LSMean) values were calculated from the measurements taken at baseline and at the end of each 4 week therapy period.p-value: 0.097Repeated Measures
Secondary
Working Memory by Corsi Block Tapping Test (CBTT)
Measures the visuo-spatial working memory span, and corresponds to the longest sequence of blocks that has been reproduced correctly at least once. Scores can range from 3 to 8, with the higher score indicating better function.
Time frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy
Population: All efficacy information is summarized and/or presented in data listings based on the Safety sample: Includes all patients who were randomized to double-blind treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Working Memory by Corsi Block Tapping Test (CBTT) | ADHD-Combined Type | 5.29 blocks correctly sequenced | Standard Error 0.22 |
| Atomoxetine | Working Memory by Corsi Block Tapping Test (CBTT) | Reading Disorder | 5.50 blocks correctly sequenced | Standard Error 0.23 |
| Atomoxetine | Working Memory by Corsi Block Tapping Test (CBTT) | ADHD-C + Reading Disorder | 5.92 blocks correctly sequenced | Standard Error 0.23 |
| Atomoxetine | Working Memory by Corsi Block Tapping Test (CBTT) | Overall | 5.57 blocks correctly sequenced | Standard Error 0.13 |
| Placebo | Working Memory by Corsi Block Tapping Test (CBTT) | Overall | 5.14 blocks correctly sequenced | Standard Error 0.13 |
| Placebo | Working Memory by Corsi Block Tapping Test (CBTT) | ADHD-Combined Type | 4.98 blocks correctly sequenced | Standard Error 0.21 |
| Placebo | Working Memory by Corsi Block Tapping Test (CBTT) | ADHD-C + Reading Disorder | 5.29 blocks correctly sequenced | Standard Error 0.23 |
| Placebo | Working Memory by Corsi Block Tapping Test (CBTT) | Reading Disorder | 5.14 blocks correctly sequenced | Standard Error 0.23 |
Comparison: Least Squares Mean (LSMean) values were calculated from the measurements taken at baseline and at the end of each 4 week therapy period.p-value: 0.003Repeated Measures