Attention Deficit Hyperactivity Disorder
Conditions
Brief summary
Double blinded clinical trial placebo controlled in 153 children (planned enrollment) with recent diagnosis of ADHD. Patients will be randomized to atomoxetine or placebo arm (2:1). The double blinded period will last 12 weeks and the treatment open phase will last up to 1 year, and atomoxetine treatment will be administered. A gatekeeper strategy will be employed for sequentially testing the secondary objectives.
Interventions
DRUGAtomoxetine Hydrochloride
DRUGplacebo
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
1. Child or adolescent patients must be at least 6 years of age, but must not yet have reached their 16th birthday prior to Visit 1, when informed consent is obtained. 2. Patients must meet the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) diagnostic criteria for ADHD. For the purposes of this study the diagnosis of ADHD will be confirmed during Visit 1 by administering the K-SADS-PL. Patients must also have an ADHDRS-IV-Parent:Inv score at least 1.5 standard deviations above the age norm for their diagnostic subtype at both Visit 1 and Visit 2. In addition, they must have a CGI-ADHD-S score 4 at both Visit 1 and Visit 2. 3. Patients must have a newly diagnosed case of ADHD. Newly diagnosed case of ADHD means that a specialist (including pediatrician, child psychiatrist, or child neurologist) or child psychologist has diagnosed ADHD (according DSM-IV-TR or International Statistical Classification of Diseases and Related Health Problems \[World Health Organisation; 10th Revision\] \[ICD 10\] criteria) within 3 months prior to Visit 1.
Exclusion criteria
1. Patients with history of ADHD diagnosis longer than 3 months prior to Visit 1. Diagnosis of ADHD means that a specialist (including pediatrician, child psychiatrist, or child neurologist) or child psychologist has diagnosed ADHD (according DSM-IV-TR or ICD 10 criteria) and has registered it in medical records or verbally informed parents about this diagnosis. 2. Patients who weigh less than 20 kg at study entry (Visit 1). If a patient's weight changes after Visit 1 to a value outside of the stated range, the patient will still be eligible, and the weight should be rounded to the nearest value within the above range for dosing purposes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 12 Week Endpoint | Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 6 Weeks | Week 6 | 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. |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 4 Weeks | Week 4 | 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. |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score Change From Week 6 to Week 12 | week 6 and week 12 | 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. |
| Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Changes From Baseline to Visit 7 (12 Weeks) | Baseline and 12 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). |
| Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Change From Baseline to Endpoint (Visit 18) of the Open-Label Extension (107 Weeks) | Baseline and Open-Label Endpoint (107 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). |
| Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Total Score Changes From Baseline to Endpoint (Week 12) | Baseline and Week 12 | The CPRS-R:S has 27 items to be completed by the parent to assess behavioral problems related to ADHD. Individual item scores range from 0 (not at all true/never/seldom: lowest impairment) to 3 (very much true/very often/very frequent: highest impairment). The total score is calculated as the sum of all items. Total scores range from 0 to 81. |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 9 Weeks | Week 9 | 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. |
| Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Baseline | The K-SADS-PL is a semi-structured interview schedule for assessing psychiatric disorders in children and adolescents. It is used to assess the status of 32 DSM-IV child and adolescent psychiatric diagnosis. |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) at 107 Weeks (Open-Label Extension) | Week 107 | 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. |
| Vital Signs - Systolic Blood Pressure | Baseline and 12 weeks | — |
| Vital Signs - Diastolic Blood Pressure | Baseline and 12 weeks | — |
| Vital Signs - Pulse | Baseline and 12 weeks | — |
| Vital Signs - Weight | Baseline and 12 weeks | — |
| Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Baseline to 12 weeks | Parent-rated assessment of a child's health status and level of functioning. It consists of 76 items. The majority of items assess frequency of activities or feelings using a five-point response format (for example, 'how good is your child at making friends?' 1=never, 5=always). Standard scores (t-value) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Standard scores are expressed in standard deviation units. T-score=\[(Score-4.2382)\*10/0.32835\]+50. Higher scores mean improvement. |
Countries
Spain
Participant flow
Pre-assignment details
158 patients enrolled during the Screening Period (Visits 1 and 2), but 7 did not receive study drug and are not included in the 151 patients randomized in the Double-Blind Period.
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine Double-Blind Acute Period: 0.5 mg/kg/day every day, by mouth for 2 weeks, 1.2 - 1.4 mg/kg/day every day, by mouth for 10 weeks Open-label Period: 1.2 - 1.4 mg/kg/day every day, by mouth for up to 1 year | 100 |
| Placebo Double-Blind Acute Period: every day, by mouth for 12 weeks,then possibility to switch to atomoxetine at 0.5 mg/kg/day every day, by mouth for 1 week Open-Label Period: 1.2 - 1.4 mg/kg/day every day, by mouth for up to 1 year | 51 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Acute Treatment | Lost to Follow-up | 0 | 1 |
| Double-Blind Acute Treatment | Non Protocol Compliance | 3 | 0 |
| Double-Blind Acute Treatment | Parent's Decision | 3 | 0 |
| Double-Blind Acute Treatment | Physician Decision | 0 | 2 |
Baseline characteristics
| Characteristic | Atomoxetine | Placebo | Total |
|---|---|---|---|
| Age Continuous | 10.3 years STANDARD_DEVIATION 2.48 | 10.3 years STANDARD_DEVIATION 2.43 | 10.3 years STANDARD_DEVIATION 2.46 |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator-Administered | 39.1 units on a scale STANDARD_DEVIATION 9 | 39.5 units on a scale STANDARD_DEVIATION 9 | 39.2 units on a scale STANDARD_DEVIATION 9 |
| Attention-Deficit/Hyperactivity Disorder Subtype Combined (Hyperactive-Inattentive) | 64 participants | 30 participants | 94.0 participants |
| Attention-Deficit/Hyperactivity Disorder Subtype Hyperactive | 5 participants | 1 participants | 6.0 participants |
| Attention-Deficit/Hyperactivity Disorder Subtype Inattentive | 30 participants | 19 participants | 49.0 participants |
| Attention-Deficit/Hyperactivity Disorder Subtype Not Assessed | 1 participants | 1 participants | 2.0 participants |
| Blood Pressure Diastolic Blood Pressure | 57.9 mmHg STANDARD_DEVIATION 7.15 | 58.0 mmHg STANDARD_DEVIATION 7.68 | 57.9 mmHg STANDARD_DEVIATION 7.31 |
| Blood Pressure Systolic Blood Pressure | 101.2 mmHg STANDARD_DEVIATION 10.01 | 100.5 mmHg STANDARD_DEVIATION 10.01 | 101.0 mmHg STANDARD_DEVIATION 9.98 |
| Body Weight | 37.9 kilograms STANDARD_DEVIATION 11.86 | 37.4 kilograms STANDARD_DEVIATION 12.18 | 37.7 kilograms STANDARD_DEVIATION 11.93 |
| Race/Ethnicity African | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity Caucasian | 98 participants | 47 participants | 145 participants |
| Race/Ethnicity Hispanic | 2 participants | 3 participants | 5 participants |
| Region of Enrollment Spain | 100 participants | 51 participants | 151 participants |
| Sex: Female, Male Female | 21 Participants | 10 Participants | 31 Participants |
| Sex: Female, Male Male | 79 Participants | 41 Participants | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 80 / 100 | 38 / 51 |
| serious Total, serious adverse events | 0 / 100 | 1 / 51 |
Outcome results
Primary
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 12 Week Endpoint
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: Week 12
Population: Intention to Treat analysis. Single item missing scores were imputed with the mean score of the remaining items when computing subscale and total scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 12 Week Endpoint | 26.3 units on a scale | Standard Deviation 12.7 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 12 Week Endpoint | 34.8 units on a scale | Standard Deviation 12.3 |
p-value: <0.00195% CI: [-11, -4.8]Mixed Models Analysis
Secondary
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) at 107 Weeks (Open-Label Extension)
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: Week 107
Population: Intention to Treat analysis. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) at 107 Weeks (Open-Label Extension) | 21.4 units on a scale | Standard Deviation 12.8 |
Secondary
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 4 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.
Time frame: Week 4
Population: Intention to Treat analysis. Single item missing scores were imputed with the mean score of the remaining items when computing subscale and total scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 4 Weeks | 31.2 units on a scale | Standard Deviation 12 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 4 Weeks | 35.5 units on a scale | Standard Deviation 12 |
Comparison: A gatekeeper strategy was employed for sequentially testing the secondary hypotheses using a REML-based Mixed-Model Repeated Measures (MMRM) technique as defined for the primary efficacy analyses. If primary hypothesis is significant at 0.05 (2-sided), first secondary hypothesis will be tested at Visit 6 from MMRM. If comparison is significant, subsequent secondary hypotheses will be tested in sequence until first null hypothesis fails to be rejected.p-value: 0.003395% CI: [-6.4, -1.3]Mixed Models Analysis
Secondary
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 6 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.
Time frame: Week 6
Population: Intention to Treat analysis. Single item missing scores were imputed with the mean score of the remaining items when computing subscale and total scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 6 Weeks | 28.7 units on a scale | Standard Deviation 12.9 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 6 Weeks | 34.4 units on a scale | Standard Deviation 12 |
Comparison: A gatekeeper strategy was employed for sequentially testing the secondary hypotheses using a REML-based Mixed-Model Repeated Measures (MMRM) technique as defined for the primary efficacy analyses. If primary hypothesis is significant at 0.05 (2-sided), first secondary hypothesis will be tested at Visit 6 from MMRM. If comparison is significant, subsequent secondary hypotheses will be tested in sequence until first null hypothesis fails to be rejected.p-value: 0.000995% CI: [-8.2, -2.2]Mixed Models Analysis
Secondary
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 9 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.
Time frame: Week 9
Population: Intention to Treat analysis. Single item missing scores were imputed with the mean score of the remaining items when computing subscale and total scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 9 Weeks | 27.3 units on a scale | Standard Deviation 12.3 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 9 Weeks | 34.4 units on a scale | Standard Deviation 12 |
Comparison: A gatekeeper strategy was employed for sequentially testing the secondary hypotheses using a REML-based Mixed-Model Repeated Measures (MMRM) technique as defined for the primary efficacy analyses. If primary hypothesis is significant at 0.05 (2-sided), first secondary hypothesis will be tested at Visit 6 from MMRM. If comparison is significant, subsequent secondary hypotheses will be tested in sequence until first null hypothesis fails to be rejected.p-value: <0.00195% CI: [-9.5, -3.6]Mixed Models Analysis
Secondary
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score Change From Week 6 to Week 12
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: week 6 and week 12
Population: Intention to Treat analysis. Single item missing scores were imputed with the mean score of the remaining items when computing subscale and total scores.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score Change From Week 6 to Week 12 | Week 6 | 28.7 units on a scale | Standard Deviation 12.9 |
| Atomoxetine | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score Change From Week 6 to Week 12 | Week 12 | 26.3 units on a scale | Standard Deviation 12.7 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score Change From Week 6 to Week 12 | Week 6 | 34.4 units on a scale | Standard Deviation 12 |
| Placebo | Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score Change From Week 6 to Week 12 | Week 12 | 34.8 units on a scale | Standard Deviation 12.3 |
Comparison: A gatekeeper strategy was employed for sequentially testing the secondary hypotheses using a REML-based Mixed-Model Repeated Measures (MMRM) technique as defined for the primary efficacy analyses. If primary hypothesis is significant at 0.05 (2-sided), first secondary hypothesis will be tested at Visit 6 from MMRM. If comparison is significant, subsequent secondary hypotheses will be tested in sequence until first null hypothesis fails to be rejected.p-value: 0.01395% CI: [-4.9, -0.6]Mixed Models Analysis
Secondary
Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks)
Parent-rated assessment of a child's health status and level of functioning. It consists of 76 items. The majority of items assess frequency of activities or feelings using a five-point response format (for example, 'how good is your child at making friends?' 1=never, 5=always). Standard scores (t-value) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Standard scores are expressed in standard deviation units. T-score=\[(Score-4.2382)\*10/0.32835\]+50. Higher scores mean improvement.
Time frame: Baseline to 12 weeks
Population: Intention to Treat analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Achievement 12 Weeks | 38.0 standard deviation units | Standard Deviation 10 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Achievement Baseline | 33.2 standard deviation units | Standard Deviation 9.5 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Satisfaction Baseline | 49.2 standard deviation units | Standard Deviation 9.2 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Satisfaction Baseline | 38.0 standard deviation units | Standard Deviation 14.9 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Comfort Baseline | 49.9 standard deviation units | Standard Deviation 9.6 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Satisfaction 12 Weeks | 40.4 standard deviation units | Standard Deviation 12.5 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Resilience Baseline | 52.0 standard deviation units | Standard Deviation 10.8 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Resilience Baseline | 42.1 standard deviation units | Standard Deviation 11.2 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Risk Avoidance Baseline | 47.6 standard deviation units | Standard Deviation 10.4 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Comfort 12 Weeks | 44.6 standard deviation units | Standard Deviation 11.4 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Achievement Baseline | 42.1 standard deviation units | Standard Deviation 10.3 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Comfort 12 Weeks | 52.7 standard deviation units | Standard Deviation 8.2 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Satisfaction 12 Weeks | 50.6 standard deviation units | Standard Deviation 9.2 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Resilience 12 Weeks | 45.3 standard deviation units | Standard Deviation 11 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Resilience 12 Weeks | 52.4 standard deviation units | Standard Deviation 9.5 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Risk Avoidance Baseline | 31.7 standard deviation units | Standard Deviation 15.8 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Risk Avoidance 12 Weeks | 51.9 standard deviation units | Standard Deviation 8.7 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Risk Avoidance 12 Weeks | 40.5 standard deviation units | Standard Deviation 14.8 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Achievement 12 Weeks | 45.5 standard deviation units | Standard Deviation 10.2 |
| Atomoxetine | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Comfort Baseline | 42.8 standard deviation units | Standard Deviation 12.5 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Achievement 12 Weeks | 45.7 standard deviation units | Standard Deviation 11.5 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Satisfaction Baseline | 39.0 standard deviation units | Standard Deviation 14.7 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Comfort Baseline | 44.4 standard deviation units | Standard Deviation 11.7 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Resilience Baseline | 41.8 standard deviation units | Standard Deviation 11.6 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Risk Avoidance Baseline | 34.1 standard deviation units | Standard Deviation 15.9 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Achievement Baseline | 33.1 standard deviation units | Standard Deviation 10.8 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Satisfaction 12 Weeks | 40.0 standard deviation units | Standard Deviation 13.8 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Comfort 12 Weeks | 44.1 standard deviation units | Standard Deviation 11.5 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Resilience 12 Weeks | 42.2 standard deviation units | Standard Deviation 10.8 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Risk Avoidance 12 Weeks | 35.9 standard deviation units | Standard Deviation 13.9 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent: Achievement 12 Weeks | 34.4 standard deviation units | Standard Deviation 10.3 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Satisfaction Baseline | 50.0 standard deviation units | Standard Deviation 12.6 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Comfort Baseline | 50.6 standard deviation units | Standard Deviation 7.9 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Resilience Baseline | 52.0 standard deviation units | Standard Deviation 11.6 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Risk Avoidance Baseline | 49.1 standard deviation units | Standard Deviation 11.3 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Achievement Baseline | 44.6 standard deviation units | Standard Deviation 10.8 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Comfort 12 Weeks | 51.9 standard deviation units | Standard Deviation 7.7 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Resilience 12 Weeks | 52.2 standard deviation units | Standard Deviation 9.4 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Risk Avoidance 12 Weeks | 49.7 standard deviation units | Standard Deviation 11.7 |
| Placebo | Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Child/Adolescent: Satisfaction 12 Weeks | 52.3 standard deviation units | Standard Deviation 11.1 |
Comparison: ANCOVA model: Dependent variable=standardized mean scores of domain at Visit 7 minus scores at Visit 1; Factors=Treatment, Investigator, Rater; Covariate=standardized mean scores of domain at Visit 1. Both treatment by rater and treatment by covariate interaction terms included in model.p-value: 0.9195% CI: [-2.59, 2.9]ANCOVA
Comparison: ANCOVA model: Dependent variable=standardized mean scores of domain at Visit 7 minus scores at Visit 1; Factors=Treatment, Investigator, Rater; Covariate=standardized mean scores of domain at Visit 1. Both treatment by rater and treatment by covariate interaction terms included in model.p-value: 0.8195% CI: [-3.39, 4.33]ANCOVA
Comparison: ANCOVA model: Dependent variable=standardized mean scores of domain at Visit 7 minus scores at Visit 1; Factors=Treatment, Investigator, Rater; Covariate=standardized mean scores of domain at Visit 1. Both treatment by rater and treatment by covariate interaction terms included in model.p-value: 0.24395% CI: [-1.35, 5.29]ANCOVA
Comparison: ANCOVA model: Dependent variable=standardized mean scores of domain at Visit 7 minus scores at Visit 1; Factors=Treatment, Investigator, Rater; Covariate=standardized mean scores of domain at Visit 1. Both treatment by rater and treatment by covariate interaction terms included in model.p-value: 0.41995% CI: [-2.26, 5.39]ANCOVA
Comparison: ANCOVA model: Dependent variable=standardized mean scores of domain at Visit 7 minus scores at Visit 1; Factors=Treatment, Investigator, Rater; Covariate=standardized mean scores of domain at Visit 1. Both treatment by rater and treatment by covariate interaction terms included in model.p-value: <0.00195% CI: [4.27, 12.55]ANCOVA
Comparison: ANCOVA model: Dependent variable=standardized mean scores of domain at Visit 7 minus scores at Visit 1; Factors=Treatment, Investigator, Rater; Covariate=standardized mean scores of domain at Visit 1. Both treatment by rater and treatment by covariate interaction terms included in model.p-value: 0.04295% CI: [0.13, 6.65]ANCOVA
Comparison: ANCOVA model: Dependent variable=standardized mean scores of domain at Visit 7 minus scores at Visit 1; Factors=Treatment, Investigator, Rater; Covariate=standardized mean scores of domain at Visit 1. Both treatment by rater and treatment by covariate interaction terms included in model.p-value: 0.32395% CI: [-4.06, 1.35]ANCOVA
Comparison: ANCOVA model: Dependent variable=standardized mean scores of domain at Visit 7 minus scores at Visit 1; Factors=Treatment, Investigator, Rater; Covariate=standardized mean scores of domain at Visit 1. Both treatment by rater and treatment by covariate interaction terms included in model.p-value: 0.45295% CI: [-1.49, 3.34]ANCOVA
Comparison: ANCOVA model: Dependent variable=standardized mean scores of domain at Visit 7 minus scores at Visit 1; Factors=Treatment, Investigator, Rater; Covariate=standardized mean scores of domain at Visit 1. Both treatment by rater and treatment by covariate interaction terms included in model.p-value: 0.00695% CI: [1.04, 6.08]ANCOVA
Comparison: ANCOVA model: Dependent variable=standardized mean scores of domain at Visit 7 minus scores at Visit 1; Factors=Treatment, Investigator, Rater; Covariate=standardized mean scores of domain at Visit 1. Both treatment by rater and treatment by covariate interaction terms included in model.p-value: 0.54195% CI: [-2.21, 4.19]ANCOVA
Secondary
Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Change From Baseline to Endpoint (Visit 18) of the Open-Label Extension (107 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).
Time frame: Baseline and Open-Label Endpoint (107 weeks)
Population: Intention to Treat analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Change From Baseline to Endpoint (Visit 18) of the Open-Label Extension (107 Weeks) | Baseline | 5.1 units on a scale | Standard Deviation 0.92 |
| Atomoxetine | Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Change From Baseline to Endpoint (Visit 18) of the Open-Label Extension (107 Weeks) | Week 107 | 3.2 units on a scale | Standard Deviation 1.28 |
Secondary
Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Changes From Baseline to Visit 7 (12 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).
Time frame: Baseline and 12 weeks
Population: Intention to Treat analysis. Single item missing scores were imputed with the mean score of the remaining items when computing subscale and total scores.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Changes From Baseline to Visit 7 (12 Weeks) | Baseline | 5.06 units on a scale | Standard Deviation 0.93 |
| Atomoxetine | Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Changes From Baseline to Visit 7 (12 Weeks) | Week 12 | 3.89 units on a scale | Standard Deviation 1.15 |
| Placebo | Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Changes From Baseline to Visit 7 (12 Weeks) | Baseline | 5.04 units on a scale | Standard Deviation 0.83 |
| Placebo | Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Changes From Baseline to Visit 7 (12 Weeks) | Week 12 | 4.5 units on a scale | Standard Deviation 0.91 |
Secondary
Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Total Score Changes From Baseline to Endpoint (Week 12)
The CPRS-R:S has 27 items to be completed by the parent to assess behavioral problems related to ADHD. Individual item scores range from 0 (not at all true/never/seldom: lowest impairment) to 3 (very much true/very often/very frequent: highest impairment). The total score is calculated as the sum of all items. Total scores range from 0 to 81.
Time frame: Baseline and Week 12
Population: Intention to Treat analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Total Score Changes From Baseline to Endpoint (Week 12) | Week 12 | 37.8 units on a scale | Standard Deviation 18.7 |
| Atomoxetine | Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Total Score Changes From Baseline to Endpoint (Week 12) | Baseline | 54.6 units on a scale | Standard Deviation 12.6 |
| Placebo | Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Total Score Changes From Baseline to Endpoint (Week 12) | Week 12 | 48.5 units on a scale | Standard Deviation 17.4 |
| Placebo | Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Total Score Changes From Baseline to Endpoint (Week 12) | Baseline | 54.7 units on a scale | Standard Deviation 13.6 |
p-value: <0.00195% CI: [-15.1, -6.2]Mixed Models Analysis
Secondary
Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL)
The K-SADS-PL is a semi-structured interview schedule for assessing psychiatric disorders in children and adolescents. It is used to assess the status of 32 DSM-IV child and adolescent psychiatric diagnosis.
Time frame: Baseline
Population: Intention to Treat analysis. All randomized participants who took at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with any Comorbidity | 46 participants |
| Atomoxetine | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with Oppositional Defiant Disorder | 28 participants |
| Atomoxetine | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with Tic Disorder | 16 participants |
| Atomoxetine | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with Affective Disorders | 3 participants |
| Atomoxetine | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with Anxiety Disorders | 13 participants |
| Atomoxetine | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with Conduct Disorder | 0 participants |
| Placebo | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with Anxiety Disorders | 6 participants |
| Placebo | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with any Comorbidity | 22 participants |
| Placebo | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with Affective Disorders | 2 participants |
| Placebo | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with Oppositional Defiant Disorder | 10 participants |
| Placebo | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with Conduct Disorder | 0 participants |
| Placebo | Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | Participants with Tic Disorder | 9 participants |
Secondary
Vital Signs - Diastolic Blood Pressure
Time frame: Baseline and 12 weeks
Population: All randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Vital Signs - Diastolic Blood Pressure | Baseline | 56.4 mmHg | Standard Deviation 9 |
| Atomoxetine | Vital Signs - Diastolic Blood Pressure | 12 Weeks | 59.3 mmHg | Standard Deviation 7.1 |
| Placebo | Vital Signs - Diastolic Blood Pressure | Baseline | 58.2 mmHg | Standard Deviation 7.2 |
| Placebo | Vital Signs - Diastolic Blood Pressure | 12 Weeks | 57.5 mmHg | Standard Deviation 8.6 |
Secondary
Vital Signs - Pulse
Time frame: Baseline and 12 weeks
Population: All randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Vital Signs - Pulse | Baseline | 75.8 beats per minute | Standard Deviation 9.8 |
| Atomoxetine | Vital Signs - Pulse | 12 Weeks | 84.5 beats per minute | Standard Deviation 12.5 |
| Placebo | Vital Signs - Pulse | Baseline | 77.0 beats per minute | Standard Deviation 9.3 |
| Placebo | Vital Signs - Pulse | 12 Weeks | 79.0 beats per minute | Standard Deviation 9.7 |
Secondary
Vital Signs - Systolic Blood Pressure
Time frame: Baseline and 12 weeks
Population: All randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Vital Signs - Systolic Blood Pressure | 12 Weeks | 102.9 mmHg | Standard Deviation 10.2 |
| Atomoxetine | Vital Signs - Systolic Blood Pressure | Baseline | 98.7 mmHg | Standard Deviation 13 |
| Placebo | Vital Signs - Systolic Blood Pressure | 12 Weeks | 101.2 mmHg | Standard Deviation 11.7 |
| Placebo | Vital Signs - Systolic Blood Pressure | Baseline | 102.2 mmHg | Standard Deviation 11.4 |
Secondary
Vital Signs - Weight
Time frame: Baseline and 12 weeks
Population: All randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Vital Signs - Weight | Baseline | 38.0 kilograms | Standard Deviation 12 |
| Atomoxetine | Vital Signs - Weight | 12 Weeks | 37.0 kilograms | Standard Deviation 11.5 |
| Placebo | Vital Signs - Weight | Baseline | 37.5 kilograms | Standard Deviation 12.3 |
| Placebo | Vital Signs - Weight | 12 Weeks | 38.9 kilograms | Standard Deviation 12.8 |