Attention Deficit Hyperactivity Disorder
Conditions
Brief summary
The purpose of the study is to investigate the relationship of changes in measures of academic performance and problem behaviors, to changes in core Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in Asian children treated with atomoxetine.
Interventions
DRUGAtomoxetine
atomoxetine 0.5 mg/kg/day once a day (QD), by mouth (PO) starting dose titrated over 1 week to target dose 1.2 mg/kg/day QD, PO for 23 weeks.
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Male or female outpatients between 8 and 11 years of age at study entry * Attention-Deficit/Hyperactivity Disorder (ADHD) meeting the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) disease diagnostic criteria * Patients who have never received medications psychotropic medications specifically to treat ADHD, or if they have received medication, that the trial of the psychotropic medication(s) was of less than 1 month duration, and occurred more than 6 months prior to study entry * Normal intelligence in the judgment of the investigator * Must be able to swallow capsules
Exclusion criteria
* Current or past history of bipolar I or II disorder, psychosis, autism, Asperger's syndrome, pervasive developmental disorder, or conduct disorder * History of seizure disorder or currently taking anticonvulsants for seizure control * Serious suicidal risk as determined by investigator * Cardiovascular disease; current or past history of hypertension * Previous treatment with atomoxetine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Change From Baseline and 24 Week Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent:Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score and School Grade Average (SGA) | Baseline, 24 weeks | Correlation was calculated between change from baseline and endpoint in ADHD-RS Total Score and change in SGA total score. ADHD-RS measures 18 symptoms associated with diagnosis of ADHD. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. SGA: Grades (0 to 100) in classes of Language, Math, and Science were obtained and average taken to get SGA Total Score between 0 and 100; higher scores indicating better grades/apptitude. Any ordinal grades were imputed to numerical grades based on communication with relevant schools. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 24 Week Endpoint in Academic Performance by School Grade Average (SGA) Total, and Separate Language, Math, and Science Scores | Baseline, 24 weeks | Separate school grades in the classes of Language, Math, and Science were obtained. A score between 0 and 100 was provided for each of the three classes, and the average taken to get a SGA Total Score between 0 and 100, with higher scores indicating better grades/apptitude in each class and overall. Any ordinal grades were imputed to numerical grades based on communication with relevant schools. |
| Change From Baseline to 24 Week Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator-Administered and Scored - Total Score | Baseline, 24 weeks | 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 scores range from 0 to 54. |
| Correlation Between Change From Baseline to 24 Week Endpoint in ADHDRS-IV-Parent:Inv Total Score and School Grade Averages in Separate Language, Math and Science Classes | Baseline, 24 weeks | Correlation was calculated between change from baseline and endpoint in ADHD-RS Total Score and change in separate SGA language, math, and science scores. ADHD-RS measures 18 symptoms associated with diagnosis of ADHD. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. SGA: separate language, math, and science school grades on a scale of 0-100, with higher scores indicating better grades/apptitude in the respective class. Any ordinal grades were imputed to numerical grades based on communication with relevant schools. |
| CGI-ADHD-Improvement Scale (CGI-ADHD-I) at 24 Week Endpoint | 24 weeks | Measures total improvement (or worsening) of a patient's ADHD symptoms from the beginning of treatment (1=very much improved, 7=very much worsened). |
| Change From Baseline to 24 Week Endpoint in Revised Conners' Parent Rating Scale: Short Form (CPRS-R:S) Attention-Deficit/Hyperactivity Disorder Index Score | Baseline, 24 weeks | A 27-item rating scale (0 \[not at all/never\] to 3 \[very much true/very often\]) completed by the parent to assess problem behaviors related to ADHD. Subscale assessed: ADHD Index. ADHD Index is the sum of items 1, 5, 7, 10, 13, 15, 17, 19, 21, 23, 25, and 27. Subscale total scores range from 0 to 36. Higher scores reflect more severe problem behaviors related to ADHD. |
| Change From Baseline to 24 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder - Severity Scale (CGI-ADHD-S) | Baseline, 24 weeks | Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients). |
Countries
China, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine 0.5 mg/kg/day once a day (QD), by mouth (PO), starting dose titrated over 1 week to target dose 1.2 mg/kg/day QD, PO for 23 weeks. | 228 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 13 |
| Overall Study | Lack of Efficacy | 5 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Patient/Caregiver Decision | 12 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Protocol Entry Criteria Not Met | 1 |
| Overall Study | Protocol Violation | 12 |
| Overall Study | Sponsor Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Atomoxetine |
|---|---|
| Age Continuous | 9.6 years STANDARD_DEVIATION 0.96 |
| Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) Total Score | 35.3 units on a scale STANDARD_DEVIATION 7.09 |
| Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) | 5.0 units on a scale STANDARD_DEVIATION 0.8 |
| Conners' Parent Rating Scale-Revised:Short Form - ADHD Index Subscale | 24.5 units on a scale STANDARD_DEVIATION 5.9 |
| Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Subtypes Combined | 141 participants |
| Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Subtypes Hyperactive | 5 participants |
| Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Subtypes Inattentive | 82 participants |
| Height | 136.4 centimeters (cm) STANDARD_DEVIATION 8.25 |
| Race/Ethnicity East Asian | 228 participants |
| Region of Enrollment China | 82 participants |
| Region of Enrollment Korea, Republic of | 70 participants |
| Region of Enrollment Taiwan | 76 participants |
| School Grade Average (SGA) Language Score | 73.8 units on a scale STANDARD_DEVIATION 18.35 |
| School Grade Average (SGA) Math Score | 72.7 units on a scale STANDARD_DEVIATION 19.89 |
| School Grade Average (SGA) Total Score | 73.9 units on a scale STANDARD_DEVIATION 15.82 |
| School Grade Score (SGA) Science Score | 75.0 units on a scale STANDARD_DEVIATION 17.04 |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 194 Participants |
| Weight | 33.3 kilograms (kg) STANDARD_DEVIATION 8 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 175 / 228 |
| serious Total, serious adverse events | 1 / 228 |
Outcome results
Primary
Correlation Between Change From Baseline and 24 Week Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent:Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score and School Grade Average (SGA)
Correlation was calculated between change from baseline and endpoint in ADHD-RS Total Score and change in SGA total score. ADHD-RS measures 18 symptoms associated with diagnosis of ADHD. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. SGA: Grades (0 to 100) in classes of Language, Math, and Science were obtained and average taken to get SGA Total Score between 0 and 100; higher scores indicating better grades/apptitude. Any ordinal grades were imputed to numerical grades based on communication with relevant schools.
Time frame: Baseline, 24 weeks
Population: All patients with baseline and at least one non-missing post-baseline score for each of the variables, regardless of them having or not having received any ordinal grades (for the SGA).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atomoxetine | Correlation Between Change From Baseline and 24 Week Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent:Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score and School Grade Average (SGA) | -0.083 Spearman Correlation Coefficient |
p-value: 0.293Spearman Partial Rank Order Correlation
Secondary
CGI-ADHD-Improvement Scale (CGI-ADHD-I) at 24 Week 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).
Time frame: 24 weeks
Population: All patients with baseline and at least one non-missing post-baseline score for each of the variables. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | CGI-ADHD-Improvement Scale (CGI-ADHD-I) at 24 Week Endpoint | 2.3 units on a scale | Standard Deviation 1.05 |
Secondary
Change From Baseline to 24 Week Endpoint in Academic Performance by School Grade Average (SGA) Total, and Separate Language, Math, and Science Scores
Separate school grades in the classes of Language, Math, and Science were obtained. A score between 0 and 100 was provided for each of the three classes, and the average taken to get a SGA Total Score between 0 and 100, with higher scores indicating better grades/apptitude in each class and overall. Any ordinal grades were imputed to numerical grades based on communication with relevant schools.
Time frame: Baseline, 24 weeks
Population: All patients with baseline and at least one non-missing post-baseline score for each of the variables. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 24 Week Endpoint in Academic Performance by School Grade Average (SGA) Total, and Separate Language, Math, and Science Scores | Change from Baseline in Language Scores | 3.9 units on a scale | Standard Deviation 13.35 |
| Atomoxetine | Change From Baseline to 24 Week Endpoint in Academic Performance by School Grade Average (SGA) Total, and Separate Language, Math, and Science Scores | Change from Baseline in Math Scores | 4.1 units on a scale | Standard Deviation 16.58 |
| Atomoxetine | Change From Baseline to 24 Week Endpoint in Academic Performance by School Grade Average (SGA) Total, and Separate Language, Math, and Science Scores | Change from Baseline in Science Scores | 6.1 units on a scale | Standard Deviation 14.98 |
| Atomoxetine | Change From Baseline to 24 Week Endpoint in Academic Performance by School Grade Average (SGA) Total, and Separate Language, Math, and Science Scores | Change from Baseline in Total Scores | 4.7 units on a scale | Standard Deviation 10.68 |
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
Secondary
Change From Baseline to 24 Week Endpoint in 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 scores range from 0 to 54.
Time frame: Baseline, 24 weeks
Population: All patients with baseline and at least one non-missing post-baseline score for each of the variables. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline to 24 Week Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator-Administered and Scored - Total Score | -18.8 units on a scale | Standard Deviation 9.27 |
p-value: <0.001Paired t-test
Secondary
Change From Baseline to 24 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder - Severity Scale (CGI-ADHD-S)
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: Baseline, 24 weeks
Population: All patients with baseline and at least one non-missing post-baseline score for each of the variables. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline to 24 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder - Severity Scale (CGI-ADHD-S) | -2.1 units on a scale | Standard Deviation 1.25 |
p-value: <0.001Paired t-test
Secondary
Change From Baseline to 24 Week Endpoint in Revised Conners' Parent Rating Scale: Short Form (CPRS-R:S) Attention-Deficit/Hyperactivity Disorder Index Score
A 27-item rating scale (0 \[not at all/never\] to 3 \[very much true/very often\]) completed by the parent to assess problem behaviors related to ADHD. Subscale assessed: ADHD Index. ADHD Index is the sum of items 1, 5, 7, 10, 13, 15, 17, 19, 21, 23, 25, and 27. Subscale total scores range from 0 to 36. Higher scores reflect more severe problem behaviors related to ADHD.
Time frame: Baseline, 24 weeks
Population: All patients with baseline and at least one non-missing post-baseline score for each of the variables. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline to 24 Week Endpoint in Revised Conners' Parent Rating Scale: Short Form (CPRS-R:S) Attention-Deficit/Hyperactivity Disorder Index Score | -9.8 units on a scale | Standard Deviation 7.94 |
p-value: <0.001Paired t-test
Secondary
Correlation Between Change From Baseline to 24 Week Endpoint in ADHDRS-IV-Parent:Inv Total Score and School Grade Averages in Separate Language, Math and Science Classes
Correlation was calculated between change from baseline and endpoint in ADHD-RS Total Score and change in separate SGA language, math, and science scores. ADHD-RS measures 18 symptoms associated with diagnosis of ADHD. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. SGA: separate language, math, and science school grades on a scale of 0-100, with higher scores indicating better grades/apptitude in the respective class. Any ordinal grades were imputed to numerical grades based on communication with relevant schools.
Time frame: Baseline, 24 weeks
Population: All patients with baseline and at least one non-missing post-baseline score for each of the variables, regardless of them having or not having received any ordinal grades (for the SGA).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Correlation Between Change From Baseline to 24 Week Endpoint in ADHDRS-IV-Parent:Inv Total Score and School Grade Averages in Separate Language, Math and Science Classes | Correlation with Language Scores | -0.086 Spearman Correlation Coefficient |
| Atomoxetine | Correlation Between Change From Baseline to 24 Week Endpoint in ADHDRS-IV-Parent:Inv Total Score and School Grade Averages in Separate Language, Math and Science Classes | Correlation with Math Scores | -0.126 Spearman Correlation Coefficient |
| Atomoxetine | Correlation Between Change From Baseline to 24 Week Endpoint in ADHDRS-IV-Parent:Inv Total Score and School Grade Averages in Separate Language, Math and Science Classes | Correlation with Science Scores | -0.058 Spearman Correlation Coefficient |
p-value: 0.276Spearman Partial Rank Order Correlation
p-value: 0.11Spearman Partial Rank Order Correlation
p-value: 0.464Spearman Partial Rank Order Correlation