Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder
Conditions
Brief summary
The study is a phase IIIb multicentre, randomised, placebo controlled, trial in paediatric patients with Attention-Deficit/Hyperactivity (ADHD) and Oppositional Defiant Disorder (ODD). The primary aim of the study is to evaluate the efficacy of atomoxetine in improving ADHD and ODD symptoms in patients non responders to a previous psychological intervention with parent support. Moreover, the potential role of atomoxetine in treating other psychiatric comorbid conditions associated with ADHD and ODD will be assessed.
Interventions
DRUGatomoxetine 0.5 mg/kg/day
atomoxetine 0.5 milligrams per kilogram per day (mg/kg/day) daily (QD), by mouth (PO)
DRUGplacebo
DRUGatomoxetine 1.2 mg/kg/day
atomoxetine 1.2 mg/kg/day QD, PO
DRUGatomoxetine 1.2-1.4 mg/kg/day
atomoxetine 1.2 - 1.4 mg/kg/day QD, PO
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
* Child or adolescent patients, male or female outpatients, who are at least 6 years of age, but must not yet have reached their 16th birthday prior to Visit 1, when informed consent is obtained. * Patients must meet Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnostic criteria for ADHD (any subtype) and ODD and score at least 1.5 standard deviations above the age norm for their diagnostic subtype using published norms for the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder (SNAP-IV ADHD) Subscale score at both Visit 1 and 2. * They must also have a SNAP-IV ODD subscale score of at least 15 at both Visit 1 and Visit 2. * Other comorbid conditions, are allowed but the diagnosis of ADHD and ODD must be the patient's primary diagnosis. * Patients must be of normal intelligence in the judgment of the investigator (that is, without a general impairment of intelligence and likely, in the investigator's judgement, to achieve a score of greater than or equal to 70 on an Intelligence Quotient (IQ) test). The administration of a formal IQ test is not an entry requirement for the study. Specific learning disabilities are not considered general impairment of intelligence.
Exclusion criteria
* Patients who weigh less than 20 kilograms (kg) at study entry (Visit 1). * Patients who have a documented history of Bipolar I or II disorder, any history of psychosis or pervasive development disorder. * Patients with a history of any seizure disorder (other than febrile seizures) or patients who have taken (or are currently taking) anticonvulsants for seizure control are not eligible to participate. * Patients at serious suicidal risk as assessed by the investigator. * Patients who, in the investigator's judgment, are likely to need psychotropic medications apart from the drug under the study, including health-food supplements that the investigator feels have central nervous system activity (for example, St. John's Wort, melatonin).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale | Visit 8 (baseline) and Visit 14 (8 weeks) | Items from the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for ADHD are included for the two subsets of symptoms: inattention (items #1-#9) and hyperactivity/impulsivity (items #11-#19). The SNAP-IV is based on a 0 (not at all) to 3 (very much) rating scale. Total subscale scores range from 0 to 54. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Visit 8 (baseline) and Visit 14 (8 weeks) | A 28-item rating scale (0 \[not at all/never\] to 3 \[very much true/very often\]) completed by the teacher to assess problem behaviors related to ADHD. Subscale total scores range from 0 to 15 for Oppositional and Cognitive Problems, 0 to 21 for Hyperactivity, and 0 to 36 for ADHD Index. |
| Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Visit 8 (baseline) and Visit 14 (8 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. Subscales: Oppositional, Cognitive Problems, Hyperactivity, and ADHD Index. Subscale total scores range from 0 to 18 for all subscales except ADHD Index which ranges from 0 to 36. |
| Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form | Visit 8 (baseline) and Visit 14 (8 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. |
| Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity | Visit 8 (baseline) and Visit 14 (8 weeks) | Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients. |
| Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale | Visit 8 (baseline) and Visit 14 (8 weeks) | Items are included from the DSM-IV criteria for Oppositional Defiant Disorder (items #21-#28). The SNAP-IV is based on a 0 (not at all) to 3 (very much) rating scale. Total subscale scores range from 0 to 24. |
| Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score | Visit 8 (baseline) and Visit 14 (8 weeks) | The scale measures symptoms of DSM-IV linked anxiety disorders in children. Contains 41 items. Individual item scores range from 0 (not true or hardly ever true) to 2 (very true or often true). Therefore, the overall score ranges from 0 to 82. Higher scores are more indicative of greater anxiety. |
| Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised | Visit 8 (baseline) and Visit 14 (8 weeks) | Measures presence and severity of depression. Consists of 17 items scored on a 1-5 or 1-7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. In general, scores below 20 indicate an absence of depression; scores of 20 or 30 indicate borderline depression; scores of 40 to 60 indicate moderate depression. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Open-Label Phase Nonserious Adverse Events | Baseline (Visit 14) though 1.5 years (Visit 20) or until atomoxetine received marketing approval | Number of participants with nonserious adverse events during the open-label phase of the trial, which was for 1.5 years or until atomoxetine received marketing approval. |
| Open-Label Phase Serious Adverse Events | Baseline (Visit 14) though 1.5 years (Visit 20) or until atomoxetine received marketing approval | Number of participants with serious adverse events during the open-label phase of the trial, which was for 1.5 years or until atomoxetine received marketing approval. |
Countries
Italy
Participant flow
Pre-assignment details
Study Period I=Screening. Study Period II=Standardized behavioral management program for parents (156 entered, 17 discontinued). Study Period III=Double-Blind (randomization). Two patients did not have post-baseline values for the primary endpoint and were not included in Baseline or efficacy analyses. Study Period IV=Optional open-label phase.
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval. | 105 |
| Placebo placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval. | 32 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period III - Double-Blind | Adverse Event | 3 | 0 |
| Period III - Double-Blind | Parent/Caregiver Decision | 2 | 0 |
| Period III - Double-Blind | Physician Decision | 2 | 0 |
| Period IV - Optional Open-Label | Adverse Event | 6 | 0 |
| Period IV - Optional Open-Label | Lack of Efficacy | 7 | 0 |
| Period IV - Optional Open-Label | Lost to Follow-up | 2 | 0 |
| Period IV - Optional Open-Label | Patient/Caregiver Decision | 46 | 0 |
| Period IV - Optional Open-Label | Physician Decision | 9 | 0 |
| Period IV - Optional Open-Label | Protocol Violation | 1 | 0 |
| Period IV - Optional Open-Label | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | Atomoxetine | Placebo | Total |
|---|---|---|---|
| Age Continuous | 9.7 years STANDARD_DEVIATION 2.2 | 10.0 years STANDARD_DEVIATION 2.4 | 9.8 years STANDARD_DEVIATION 2.3 |
| Height | 140.1 centimeters STANDARD_DEVIATION 15.2 | 141.6 centimeters STANDARD_DEVIATION 15.3 | 140.4 centimeters STANDARD_DEVIATION 15.1 |
| Race/Ethnicity Caucasian | 104 participants | 29 participants | 133 participants |
| Race/Ethnicity Hispanic | 1 participants | 3 participants | 4 participants |
| Region of Enrollment Italy | 105 participants | 32 participants | 137 participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 98 Participants | 29 Participants | 127 Participants |
| Weight | 39.3 kilograms STANDARD_DEVIATION 15.8 | 41.4 kilograms STANDARD_DEVIATION 14.1 | 39.8 kilograms STANDARD_DEVIATION 15.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 79 / 107 | 12 / 32 |
| serious Total, serious adverse events | 0 / 107 | 0 / 32 |
Outcome results
Primary
Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale
Items from the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for ADHD are included for the two subsets of symptoms: inattention (items #1-#9) and hyperactivity/impulsivity (items #11-#19). The SNAP-IV is based on a 0 (not at all) to 3 (very much) rating scale. Total subscale scores range from 0 to 54.
Time frame: Visit 8 (baseline) and Visit 14 (8 weeks)
Population: Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e, 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale | Baseline | 42.7 units on a scale | Standard Deviation 6.2 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale | Change to 8 Week Endpoint | -8.1 units on a scale | Standard Deviation 9.2 |
| Placebo | Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale | Baseline | 41.5 units on a scale | Standard Deviation 6.9 |
| Placebo | Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale | Change to 8 Week Endpoint | -2.0 units on a scale | Standard Deviation 4.7 |
Comparison: Using an estimate of the common standard deviation of 13 points, the planned sample size will give about 80% power to detect a difference between the groups of 8 points on the SNAP-IV. The sample size was determined using a two-sided test with p=0.05, and assumes that up to 10% of patients will discontinue the study without providing post-baseline efficacy data in Study Period III.p-value: <0.001ANCOVA
Secondary
Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form
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: Visit 8 (baseline) and Visit 14 (8 weeks)
Population: Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e., 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied. Missing data were not imputed, which generates different analysis population sizes for the different endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form | Baseline | 27.1 standard deviation units | Standard Deviation 10.4 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form | Change to 8 Week Endpoint | 3.6 standard deviation units | Standard Deviation 8 |
| Placebo | Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form | Baseline | 26.9 standard deviation units | Standard Deviation 11.2 |
| Placebo | Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form | Change to 8 Week Endpoint | 1.2 standard deviation units | Standard Deviation 6.6 |
p-value: 0.071ANCOVA
Secondary
Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised
Measures presence and severity of depression. Consists of 17 items scored on a 1-5 or 1-7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. In general, scores below 20 indicate an absence of depression; scores of 20 or 30 indicate borderline depression; scores of 40 to 60 indicate moderate depression.
Time frame: Visit 8 (baseline) and Visit 14 (8 weeks)
Population: Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e, 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised | Baseline | 28.0 units on a scale | Standard Deviation 8.4 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised | Change to 8 Week Endpoint | -0.5 units on a scale | Standard Deviation 4.4 |
| Placebo | Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised | Baseline | 26.9 units on a scale | Standard Deviation 8.1 |
| Placebo | Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised | Change to 8 Week Endpoint | -0.1 units on a scale | Standard Deviation 5 |
p-value: 0.87ANCOVA
Secondary
Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity
Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients.
Time frame: Visit 8 (baseline) and Visit 14 (8 weeks)
Population: Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e, 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity | Baseline | 5.1 units on a scale | Standard Deviation 0.8 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity | Change to 8 Week Endpoint | -0.6 units on a scale | Standard Deviation 0.7 |
| Placebo | Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity | Baseline | 5.1 units on a scale | Standard Deviation 0.9 |
| Placebo | Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity | Change to 8 Week Endpoint | 0.0 units on a scale | Standard Deviation 0.5 |
p-value: <0.001ANCOVA
Secondary
Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores
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. Subscales: Oppositional, Cognitive Problems, Hyperactivity, and ADHD Index. Subscale total scores range from 0 to 18 for all subscales except ADHD Index which ranges from 0 to 36.
Time frame: Visit 8 (baseline) and Visit 14 (8 weeks)
Population: Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e., 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied. Missing data were not imputed, which generates different analysis population sizes for the different endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | ADHD Index Change to 8 Week Endpoint | -5.0 units on a scale | Standard Deviation 6.7 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Cognitive Problems Baseline | 14.3 units on a scale | Standard Deviation 3.1 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Hyperactivity Baseline | 12.0 units on a scale | Standard Deviation 3.8 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Hyperactivity Change to 8 Week Endpoint | -2.2 units on a scale | Standard Deviation 4.1 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Oppositional Baseline | 11.7 units on a scale | Standard Deviation 3.8 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Oppositional Change to 8 Week Endpoint | -1.2 units on a scale | Standard Deviation 3.9 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Cognitive Problems Change to 8 Week Endpoint | -2.3 units on a scale | Standard Deviation 3.8 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | ADHD Index Baseline | 28.2 units on a scale | Standard Deviation 4.9 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Hyperactivity Baseline | 12.0 units on a scale | Standard Deviation 4 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Oppositional Baseline | 12.2 units on a scale | Standard Deviation 3.9 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Cognitive Problems Baseline | 14.2 units on a scale | Standard Deviation 3.2 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Cognitive Problems Change to 8 Week Endpoint | 0.2 units on a scale | Standard Deviation 2.6 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Oppositional Change to 8 Week Endpoint | 0.8 units on a scale | Standard Deviation 2.7 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | ADHD Index Baseline | 28.4 units on a scale | Standard Deviation 5.2 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | Hyperactivity Change to 8 Week Endpoint | -0.7 units on a scale | Standard Deviation 2.6 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores | ADHD Index Change to 8 Week Endpoint | -0.1 units on a scale | Standard Deviation 3.9 |
p-value: 0.002ANCOVA
p-value: <0.001ANCOVA
p-value: 0.022ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores
A 28-item rating scale (0 \[not at all/never\] to 3 \[very much true/very often\]) completed by the teacher to assess problem behaviors related to ADHD. Subscale total scores range from 0 to 15 for Oppositional and Cognitive Problems, 0 to 21 for Hyperactivity, and 0 to 36 for ADHD Index.
Time frame: Visit 8 (baseline) and Visit 14 (8 weeks)
Population: Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e., 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied. Missing data were not imputed, which generates different analysis population sizes for the different endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Oppositional Change to 8 Week Endpoint | -1.1 units on a scale | Standard Deviation 2.9 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Hyperactivity Change to 8 Week Endpoint | -2.1 units on a scale | Standard Deviation 4.7 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Cognitive Problems Change to 8 Week Endpoint | -0.9 units on a scale | Standard Deviation 2.5 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | ADHD Index Baseline | 25.3 units on a scale | Standard Deviation 8.4 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Cognitive Problems Baseline | 8.2 units on a scale | Standard Deviation 4.3 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | ADHD Index Change to 8 Week Endpoint | -3.5 units on a scale | Standard Deviation 7.1 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Hyperactivity Baseline | 12.8 units on a scale | Standard Deviation 5.5 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Oppositional Baseline | 7.6 units on a scale | Standard Deviation 4.3 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Hyperactivity Baseline | 16.3 units on a scale | Standard Deviation 3.4 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Oppositional Change to 8 Week Endpoint | 0.1 units on a scale | Standard Deviation 2.2 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Cognitive Problems Baseline | 8.5 units on a scale | Standard Deviation 3.7 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Cognitive Problems Change to 8 Week Endpoint | 0.0 units on a scale | Standard Deviation 1.7 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Oppositional Baseline | 10.8 units on a scale | Standard Deviation 3.8 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | Hyperactivity Change to 8 Week Endpoint | -1.1 units on a scale | Standard Deviation 3 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | ADHD Index Baseline | 29.4 units on a scale | Standard Deviation 6 |
| Placebo | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores | ADHD Index Change to 8 Week Endpoint | -0.9 units on a scale | Standard Deviation 3.3 |
p-value: 0.002ANCOVA
p-value: 0.113ANCOVA
p-value: 0.051ANCOVA
p-value: 0.061ANCOVA
Secondary
Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score
The scale measures symptoms of DSM-IV linked anxiety disorders in children. Contains 41 items. Individual item scores range from 0 (not true or hardly ever true) to 2 (very true or often true). Therefore, the overall score ranges from 0 to 82. Higher scores are more indicative of greater anxiety.
Time frame: Visit 8 (baseline) and Visit 14 (8 weeks)
Population: Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e., 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied. Missing data were not imputed, which generates different analysis population sizes for the different endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score | Baseline | 20.3 units on a scale | Standard Deviation 11.8 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score | Change to 8 Week Endpoint | -2.1 units on a scale | Standard Deviation 7.6 |
| Placebo | Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score | Baseline | 18.8 units on a scale | Standard Deviation 11.5 |
| Placebo | Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score | Change to 8 Week Endpoint | -1.7 units on a scale | Standard Deviation 6.5 |
p-value: 0.836ANCOVA
Secondary
Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale
Items are included from the DSM-IV criteria for Oppositional Defiant Disorder (items #21-#28). The SNAP-IV is based on a 0 (not at all) to 3 (very much) rating scale. Total subscale scores range from 0 to 24.
Time frame: Visit 8 (baseline) and Visit 14 (8 weeks)
Population: Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e, 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale | Change to 8 Week Endpoint | -2.7 units on a scale | Standard Deviation 4.1 |
| Atomoxetine | Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale | Baseline | 17.2 units on a scale | Standard Deviation 3 |
| Placebo | Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale | Baseline | 17.5 units on a scale | Standard Deviation 3.8 |
| Placebo | Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale | Change to 8 Week Endpoint | -0.3 units on a scale | Standard Deviation 2.6 |
p-value: 0.001ANCOVA
Other Pre-specified
Open-Label Phase Nonserious Adverse Events
Number of participants with nonserious adverse events during the open-label phase of the trial, which was for 1.5 years or until atomoxetine received marketing approval.
Time frame: Baseline (Visit 14) though 1.5 years (Visit 20) or until atomoxetine received marketing approval
Population: Number of patients who entered this optional open-label phase. All of the patients were dispensed drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Abdominal pain | 6 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Nausea | 10 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Vomiting | 11 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Pyrexia | 6 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Influenza | 7 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Weight decreased | 5 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Anorexia | 10 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Agitation | 7 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Insomnia | 4 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Decreased appetite | 7 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Headache | 19 participants |
| Atomoxetine | Open-Label Phase Nonserious Adverse Events | Somnolence | 8 participants |
Other Pre-specified
Open-Label Phase Serious Adverse Events
Number of participants with serious adverse events during the open-label phase of the trial, which was for 1.5 years or until atomoxetine received marketing approval.
Time frame: Baseline (Visit 14) though 1.5 years (Visit 20) or until atomoxetine received marketing approval
Population: Number of patients who entered this optional open-label phase. All of the patients were dispensed drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Open-Label Phase Serious Adverse Events | Vomiting | 1 participants |
| Atomoxetine | Open-Label Phase Serious Adverse Events | Infectious mononucleosis | 1 participants |
| Atomoxetine | Open-Label Phase Serious Adverse Events | Agitation | 1 participants |