Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder
Conditions
Brief summary
A three-arm, randomized, double-blind, placebo-controlled, Phase 4, multicenter study to compare the efficacy and safety of atomoxetine versus placebo in children and adolescents aged 6 through 17 years with attention-deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) who are treated as outpatients in Germany. After an initial 3- to 28-day screening and washout phase, participants will be assigned to double-blind treatment with atomoxetine or placebo. A 2 week up-titration period will be succeeded by a 7 week treatment period at the target dose. The primary efficacy measure will be the Swanson, Nolan and Pelham Rating Scale Revised (SNAP-IV) ODD subscale score.
Interventions
DRUGAtomoxetine
Dosage form for the atomoxetine fast and slow titration arms consists of 2.5 mg, 10 mg, 20 mg, 25 mg, and 40 mg capsules. Double-blind treatment will consist of 3 capsules taken once per day for approximately 9 weeks.
DRUGPlacebo
Double-blind treatment will consist of 3 matching placebo capsules taken once per day by mouth for approximately 9 weeks.
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 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female outpatients who are at least 6 years of age, and who will not have reached their 18th birthday * Diagnosis of ADHD and presence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria A through C for ODD (NOTE: diagnosis for conduct disorder not exclusionary) * Normal intelligence * Able to swallow capsules
Exclusion criteria
* Weigh less than 20 kilogram (kg) or more than 90 kg at study entry * Prior treatment with atomoxetine * History of seizure disorder, suicidal risk, alcohol or drug abuse within the past 3 months * History of severe allergies or multiple adverse drug reactions * Cardiovascular disorders: hypertension, unexplained cardiac signs or symptoms, QT (measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle) prolongation , inherited cardiac disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Swanson, Nolan and Pelham Rating Scale Revised (SNAP-IV) Oppositional Defiant Disorder: (ODD) Score | 9 weeks | The SNAP-IV, a 26-item scale, includes 1 item for each of the 18 symptoms contained in the DSM-IV diagnosis of ADHD and 1 item for each of the 8 symptoms contained in the DSM-IV diagnosis of ODD. Each item is scored on a 0 to 3 scale (0=Not at All, 1=Just a Little, 2=Pretty Much, 3=Very Much). The SNAP-IV yields scores in three domains: Inattention (items 1-9: subscore range=0-27), Hyperact-ivity/Impulsivity (items 10-18: subscale range=0-27), and Oppositional (items 19-26: subscale range=0-24). SNAP-IV: ADHD Combined Scale score (inattention + hyperactivity/impulsivity) ranges from 0-54. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Inattention Score | 9 weeks | The SNAP-IV: ADHD Inattention Subscale (items 1-9) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 27. |
| Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): Hyperactivity/Impulsivity Score | 9 weeks | The SNAP-IV: ADHD Hyperactivity/Impulsivity Subscale (items 10-18) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 27. |
| Parent-Rated Attention-Deficit Scale (FBB-HKS), Total Score: Severity | 9 weeks | FBB-HKS (Fremdbeurteilungsbogen fur Hyperkinetische Storungen), the German, parent-rated scale for attention-deficit, is a 20-item rating scale which describes ADHD symptom criteria of DSM-IV and is grouped based upon the 3 ADHD domains: inattention (items 1-9); hyperactivity (items 10-16); impulsivity (items 17-20). Parents rated symptom severity of each item during the last 7 days on a 0 to 3 scale (0=not at all to 3=very much). The total score was calculated for ADHD overall (sum of ratings for items 1-20, divided by 20). Higher scores indicate higher severity of symptoms. |
| Parent-Rated Oppositional Defiant/Conduct Disorders Scale (FBB-SSV): Total Score, Severity | 9 weeks | FBB-SSV (Fremdbeurteilungsbogen fur Storungen des Sozialverhaltens), the German, parent-rated oppositional defiant/conduct disorders scale, covers 23 criteria for ODD and 25 for conduct disorder (CD) in four sections. Parents rated symptom severity of each item during the last 7 days on a 0 to 3 scale (0=not at all to 3=very much). The total score was calculated for ODD/CD overall (sum of ratings for items 1-17, divided by 17). Higher scores indicate higher severity of symptoms. |
| Investigator-Rated Individual Target Behaviors (ITB-Inv): Intensity Score | 9 weeks | ITB-Inv assesses frequency and intensity of individually-defined target behaviors. The investigator defines 3 individual behavior problems based on interviews and additional information. Those most impairing for the child or stressful for the parents will be chosen as target behavior. Intensity during the last 7 days is rated on a 10-point scale (0=no problems to 9=most severe problems) with the lowest possible score of 0 and the highest possible of 27. |
| Investigator-Rated Individual Target Behaviors (ITB-Inv): Frequency Score | 9 weeks | ITB-Inv assesses frequency and intensity of individually-defined target behaviors. The investigator defines 3 individual behavior problems based on interviews and additional information. Those most impairing for the child or stressful for the parents will be chosen as target behavior. Frequency of each target behavior during the last 7 days is rated on a 6-point scale (0=never to 5=always) with 0 as lowest possible score and 15 the highest possible score. |
| Impact on Family Scale (FaBel), Total Impact Score | 9 weeks | Family burden is assessed by the FaBel questionnaire (German version of the Impact on Family Scale). Questionnaire is answered by participant's caregiver and contains 33 Likert-scaled items to assess general negative impact (of a disability, disorder, disease) on parents, description of social relationships, concern for siblings, financial impact, problems in coping as well as a total score. Each item is rated on a 4-point scale (1=fully applies, 4=applies not at all). Total scores range from 24-96. Higher scores correspond to higher family burden. |
| Clinical Global Impressions - Severity (CGI-S): ADHD Score | 9 weeks | The physician-rated CGI-S ADHD measures the participant's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients) during the last 7 days. |
| Clinical Global Impressions - Severity (CGI-S): ODD Score | 9 weeks | The physician-rated CGI-S ODD measures the participant's overall severity of ODD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients) during the last 7 days. |
| Clinical Global Impressions - Severity (CGI-S): Combined ADHD and ODD Scores | 9 weeks | The physician-rated CGI-S Combined ADHD and ODD measures the participant's overall severity of both ADHD and ODD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients) during the last 7 days. |
| Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Combined Score | 9 weeks | The SNAP-IV: ADHD Combined Subscale for inattention (items 1-9) and hyperactivity/impulsivity (items 11-19) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 54. |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Physical Well-Being Score | 9 weeks | KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the Physical Well-Being subscale is 0; highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL. |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Emotional Well-Being Score | 9 weeks | KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time).The lowest possible score for the Emotional Well-Being subscale is 0; highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL. |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Self Esteem Score | 9 weeks | KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the Self Esteem subscale is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL. |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Family Score | 9 weeks | KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1=never; 5=all the time). The lowest possible score on the Family subscale is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL. |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Friends Score | 9 weeks | KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the Friends subscale is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL. |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): School Score | 9 weeks | KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the School subscore is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL. |
| Number of Participants Discontinuing Treatment | 9 weeks | Originally, time to treatment discontinuation was analyzed, deeming participants 'censored' if they reached the end of the observation period, were lost to followup, or withdrew informed consent. Because the median was not reached, the number of participants who discontinued (i.e., those who were not censored) is reported here. |
| Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | 3 weeks | Number of participants who experienced pre-specified categories of clinically relevant adverse events during the initial three-weeks of study treatment. NOTE: this is a subset of the overall adverse events which are reported by participant and event. |
| Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | 9 weeks | Number of participants who experienced pre-specified categories of clinically relevant adverse events during the nine-week study treatment period. NOTE: this is a subset of the overall adverse events which are reported by participant and event. |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Total Quality of Life Score | 9 weeks | KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score in the Total QOL score is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher score indicates better QOL. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine Fast Titration 0.5 milligram per kilogram (mg/kg) daily dose taken orally for 1 week, then 1.2 mg/kg daily dose taken orally for 8 weeks | 60 |
| Atomoxetine Slow Titration 0.5 mg/kg daily dose taken orally for 1 week, then 0.8 mg/kg daily dose taken orally for 1 week, then 1.2 mg/kg daily dose taken orally for 7 weeks | 61 |
| Placebo matching placebo daily dose taken orally | 59 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| All Randomized and Treated Patients | Adverse Event | 6 | 2 | 1 |
| All Randomized and Treated Patients | Lack of Efficacy | 7 | 4 | 17 |
| All Randomized and Treated Patients | Parent/Caregiver Decision | 2 | 6 | 1 |
| All Randomized and Treated Patients | Physician Decision | 0 | 0 | 1 |
| All Randomized and Treated Patients | Withdrawal by Subject | 1 | 1 | 2 |
| All Randomized Patients | Protocol Violation | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Atomoxetine Fast Titration | Atomoxetine Slow Titration | Placebo |
|---|---|---|---|---|
| Age Continuous | 11.0 years STANDARD_DEVIATION 3.01 | 11.1 years STANDARD_DEVIATION 2.88 | 10.8 years STANDARD_DEVIATION 3.39 | 11.1 years STANDARD_DEVIATION 2.77 |
| Clinical Global Impressions - Severity (CGI-S): ADHD Score | 5.1 units on a scale STANDARD_DEVIATION 0.77 | 5.0 units on a scale STANDARD_DEVIATION 0.77 | 5.2 units on a scale STANDARD_DEVIATION 0.79 | 5.1 units on a scale STANDARD_DEVIATION 0.74 |
| Clinical Global Impressions - Severity (CGI-S): Combined ADHD and ODD Scores | 5.1 units on a scale STANDARD_DEVIATION 0.76 | 4.9 units on a scale STANDARD_DEVIATION 0.77 | 5.4 units on a scale STANDARD_DEVIATION 0.73 | 5.1 units on a scale STANDARD_DEVIATION 0.71 |
| Clinical Global Impressions - Severity (CGI-S): ODD Score | 5.1 units on a scale STANDARD_DEVIATION 0.88 | 4.9 units on a scale STANDARD_DEVIATION 0.92 | 5.3 units on a scale STANDARD_DEVIATION 0.83 | 5.0 units on a scale STANDARD_DEVIATION 0.86 |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Emotional Well-Being Score | 71.9 units on a scale STANDARD_DEVIATION 17.22 | 72.9 units on a scale STANDARD_DEVIATION 18.58 | 72.5 units on a scale STANDARD_DEVIATION 17.28 | 70.1 units on a scale STANDARD_DEVIATION 15.92 |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Family Score | 56.2 units on a scale STANDARD_DEVIATION 20.55 | 58.7 units on a scale STANDARD_DEVIATION 20.17 | 57.6 units on a scale STANDARD_DEVIATION 20.73 | 52.3 units on a scale STANDARD_DEVIATION 20.5 |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Friends Score | 55.4 units on a scale STANDARD_DEVIATION 22.02 | 58.2 units on a scale STANDARD_DEVIATION 21.56 | 53.9 units on a scale STANDARD_DEVIATION 21.23 | 54.2 units on a scale STANDARD_DEVIATION 23.34 |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Physical Well-Being Score | 79.0 units on a scale STANDARD_DEVIATION 18.54 | 79.8 units on a scale STANDARD_DEVIATION 18.53 | 75.9 units on a scale STANDARD_DEVIATION 19.99 | 81.5 units on a scale STANDARD_DEVIATION 16.78 |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): School Score | 62.0 units on a scale STANDARD_DEVIATION 17.5 | 62.2 units on a scale STANDARD_DEVIATION 16.74 | 61.5 units on a scale STANDARD_DEVIATION 20.62 | 62.4 units on a scale STANDARD_DEVIATION 15.06 |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Self Esteem Score | 52.6 units on a scale STANDARD_DEVIATION 18.71 | 55.4 units on a scale STANDARD_DEVIATION 18.48 | 52.0 units on a scale STANDARD_DEVIATION 18.71 | 50.4 units on a scale STANDARD_DEVIATION 18.92 |
| German Revised Children's Quality of Life Questionnaire (KINDL-R): Total Quality of Life Score | 62.9 units on a scale STANDARD_DEVIATION 12.78 | 64.5 units on a scale STANDARD_DEVIATION 12.43 | 62.4 units on a scale STANDARD_DEVIATION 12.92 | 61.8 units on a scale STANDARD_DEVIATION 13.02 |
| Impact on Family Scale (FaBel): Total Impact Score | 53.8 units on a scale STANDARD_DEVIATION 12.89 | 53.3 units on a scale STANDARD_DEVIATION 12.88 | 54.1 units on a scale STANDARD_DEVIATION 13.15 | 53.9 units on a scale STANDARD_DEVIATION 12.83 |
| Investigator-Rated Individual Target Behaviors (ITB-Inv): Frequency Score | 11.2 units on a scale STANDARD_DEVIATION 2.27 | 10.9 units on a scale STANDARD_DEVIATION 2.03 | 11.4 units on a scale STANDARD_DEVIATION 2.06 | 11.3 units on a scale STANDARD_DEVIATION 2.67 |
| Investigator-Rated Individual Target Behaviors (ITB-Inv): Intensity Score | 21.3 units on a scale STANDARD_DEVIATION 3.56 | 21.3 units on a scale STANDARD_DEVIATION 3.62 | 22.1 units on a scale STANDARD_DEVIATION 3.39 | 20.5 units on a scale STANDARD_DEVIATION 3.57 |
| Parent-Rated Attention-Deficit Scale (FBB-HKS): Total Score, Severity | 2.0 units on a scale STANDARD_DEVIATION 0.56 | 2.0 units on a scale STANDARD_DEVIATION 0.62 | 2.0 units on a scale STANDARD_DEVIATION 0.54 | 1.9 units on a scale STANDARD_DEVIATION 0.52 |
| Parent-Rated Oppositional Defiant/Conduct Disorders Scale (FBB-SSV): Total Score, Severity | 1.4 units on a scale STANDARD_DEVIATION 0.52 | 1.4 units on a scale STANDARD_DEVIATION 0.53 | 1.4 units on a scale STANDARD_DEVIATION 0.49 | 1.4 units on a scale STANDARD_DEVIATION 0.56 |
| Prior Therapy: Attention-Deficit/Hyperactive Disorder (ADHD), Oppositional Defiant Disorder (ODD) Previous non-drug treatment | 24 participants | 6 participants | 9 participants | 9 participants |
| Prior Therapy: Attention-Deficit/Hyperactive Disorder (ADHD), Oppositional Defiant Disorder (ODD) Previous psychotherapy | 20 participants | 8 participants | 7 participants | 5 participants |
| Prior Therapy: Attention-Deficit/Hyperactive Disorder (ADHD), Oppositional Defiant Disorder (ODD) Previous psychotropic medication | 6 participants | 3 participants | 0 participants | 3 participants |
| Prior Therapy: Attention-Deficit/Hyperactive Disorder (ADHD), Oppositional Defiant Disorder (ODD) Previous treatment with stimulants | 80 participants | 23 participants | 28 participants | 29 participants |
| Race/Ethnicity, Customized African | 2 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 178 participants | 60 participants | 60 participants | 58 participants |
| Region of Enrollment Germany | 180 participants | 60 participants | 61 participants | 59 participants |
| Sex: Female, Male Female | 28 Participants | 9 Participants | 8 Participants | 11 Participants |
| Sex: Female, Male Male | 152 Participants | 51 Participants | 53 Participants | 48 Participants |
| Summary of ADHD Diagnosis ADHD - combined type | 136 participants | 44 participants | 45 participants | 47 participants |
| Summary of ADHD Diagnosis ADHD - predominantly hyperactive-impulsive type | 9 participants | 3 participants | 2 participants | 4 participants |
| Summary of ADHD Diagnosis ADHD - predominantly inattentive type | 35 participants | 13 participants | 14 participants | 8 participants |
| Summary of ODD Diagnosis Adjustment disorder, emotion, conduct disturbance | 1 participants | 1 participants | 0 participants | 0 participants |
| Summary of ODD Diagnosis Conduct disorder | 44 participants | 14 participants | 16 participants | 14 participants |
| Summary of ODD Diagnosis Disruptive behavior disorder not specified | 1 participants | 1 participants | 0 participants | 0 participants |
| Summary of ODD Diagnosis Oppositional defiant disorder | 134 participants | 44 participants | 45 participants | 45 participants |
| Swanson, Nolan & Pelham Rating Scale-Revised (SNAP-IV): ADHD Combined Score | 37.3 units on a scale STANDARD_DEVIATION 9.28 | 37.6 units on a scale STANDARD_DEVIATION 9.7 | 38.0 units on a scale STANDARD_DEVIATION 8.91 | 36.4 units on a scale STANDARD_DEVIATION 9.31 |
| Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Inattention Subscale Score | 17.9 units on a scale STANDARD_DEVIATION 5.01 | 17.7 units on a scale STANDARD_DEVIATION 5.23 | 18.3 units on a scale STANDARD_DEVIATION 4.91 | 17.5 units on a scale STANDARD_DEVIATION 4.94 |
| Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): Hyperactivity/Impulsivity Score | 19.5 units on a scale STANDARD_DEVIATION 4.85 | 19.9 units on a scale STANDARD_DEVIATION 4.98 | 19.7 units on a scale STANDARD_DEVIATION 4.76 | 18.9 units on a scale STANDARD_DEVIATION 4.85 |
| Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ODD Score | 15.5 units on a scale STANDARD_DEVIATION 4.35 | 15.5 units on a scale STANDARD_DEVIATION 4.07 | 15.6 units on a scale STANDARD_DEVIATION 3.82 | 15.6 units on a scale STANDARD_DEVIATION 5.13 |
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 | 48 / 60 | 43 / 61 | 32 / 59 |
| serious Total, serious adverse events | 1 / 60 | 1 / 61 | 1 / 59 |
Outcome results
Primary
Swanson, Nolan and Pelham Rating Scale Revised (SNAP-IV) Oppositional Defiant Disorder: (ODD) Score
The SNAP-IV, a 26-item scale, includes 1 item for each of the 18 symptoms contained in the DSM-IV diagnosis of ADHD and 1 item for each of the 8 symptoms contained in the DSM-IV diagnosis of ODD. Each item is scored on a 0 to 3 scale (0=Not at All, 1=Just a Little, 2=Pretty Much, 3=Very Much). The SNAP-IV yields scores in three domains: Inattention (items 1-9: subscore range=0-27), Hyperact-ivity/Impulsivity (items 10-18: subscale range=0-27), and Oppositional (items 19-26: subscale range=0-24). SNAP-IV: ADHD Combined Scale score (inattention + hyperactivity/impulsivity) ranges from 0-54.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Swanson, Nolan and Pelham Rating Scale Revised (SNAP-IV) Oppositional Defiant Disorder: (ODD) Score | 8.6 units on a scale | Standard Error 0.7 |
| Atomoxetine Slow Titration | Swanson, Nolan and Pelham Rating Scale Revised (SNAP-IV) Oppositional Defiant Disorder: (ODD) Score | 9.0 units on a scale | Standard Error 0.7 |
| Placebo | Swanson, Nolan and Pelham Rating Scale Revised (SNAP-IV) Oppositional Defiant Disorder: (ODD) Score | 12.0 units on a scale | Standard Error 0.7 |
p-value: <0.00195% CI: [-5, -1.5]Mixed Models Analysis
Secondary
Clinical Global Impressions - Severity (CGI-S): ADHD Score
The physician-rated CGI-S ADHD measures the participant's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients) during the last 7 days.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Clinical Global Impressions - Severity (CGI-S): ADHD Score | 3.5 units on a scale | Standard Error 0.1 |
| Atomoxetine Slow Titration | Clinical Global Impressions - Severity (CGI-S): ADHD Score | 3.6 units on a scale | Standard Error 0.1 |
| Placebo | Clinical Global Impressions - Severity (CGI-S): ADHD Score | 4.3 units on a scale | Standard Error 0.1 |
p-value: <0.00195% CI: [-1.1, -0.4]Mixed Models Analysis
Secondary
Clinical Global Impressions - Severity (CGI-S): Combined ADHD and ODD Scores
The physician-rated CGI-S Combined ADHD and ODD measures the participant's overall severity of both ADHD and ODD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients) during the last 7 days.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Clinical Global Impressions - Severity (CGI-S): Combined ADHD and ODD Scores | 3.7 units on a scale | Standard Error 0.1 |
| Atomoxetine Slow Titration | Clinical Global Impressions - Severity (CGI-S): Combined ADHD and ODD Scores | 3.5 units on a scale | Standard Error 0.1 |
| Placebo | Clinical Global Impressions - Severity (CGI-S): Combined ADHD and ODD Scores | 4.4 units on a scale | Standard Error 0.1 |
p-value: <0.00195% CI: [-1.1, -0.4]Mixed Models Analysis
Secondary
Clinical Global Impressions - Severity (CGI-S): ODD Score
The physician-rated CGI-S ODD measures the participant's overall severity of ODD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients) during the last 7 days.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Clinical Global Impressions - Severity (CGI-S): ODD Score | 3.6 units on a scale | Standard Error 0.2 |
| Atomoxetine Slow Titration | Clinical Global Impressions - Severity (CGI-S): ODD Score | 3.5 units on a scale | Standard Error 0.1 |
| Placebo | Clinical Global Impressions - Severity (CGI-S): ODD Score | 4.3 units on a scale | Standard Error 0.2 |
p-value: <0.00195% CI: [-1.1, -0.4]Mixed Models Analysis
Secondary
German Revised Children's Quality of Life Questionnaire (KINDL-R): Emotional Well-Being Score
KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time).The lowest possible score for the Emotional Well-Being subscale is 0; highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Emotional Well-Being Score | 71.8 units on a scale | Standard Error 2.3 |
| Atomoxetine Slow Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Emotional Well-Being Score | 73.0 units on a scale | Standard Error 2.3 |
| Placebo | German Revised Children's Quality of Life Questionnaire (KINDL-R): Emotional Well-Being Score | 66.9 units on a scale | Standard Error 2.3 |
p-value: 0.0595% CI: [0, 10.9]ANCOVA
Secondary
German Revised Children's Quality of Life Questionnaire (KINDL-R): Family Score
KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1=never; 5=all the time). The lowest possible score on the Family subscale is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Family Score | 63.7 units on a scale | Standard Error 2.8 |
| Atomoxetine Slow Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Family Score | 61.9 units on a scale | Standard Error 2.7 |
| Placebo | German Revised Children's Quality of Life Questionnaire (KINDL-R): Family Score | 54.7 units on a scale | Standard Error 2.7 |
p-value: 0.01595% CI: [1.6, 14.6]ANCOVA
Secondary
German Revised Children's Quality of Life Questionnaire (KINDL-R): Friends Score
KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the Friends subscale is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Friends Score | 67.1 units on a scale | Standard Error 2.8 |
| Atomoxetine Slow Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Friends Score | 61.3 units on a scale | Standard Error 2.8 |
| Placebo | German Revised Children's Quality of Life Questionnaire (KINDL-R): Friends Score | 56.2 units on a scale | Standard Error 2.8 |
p-value: 0.01895% CI: [1.4, 14.7]ANCOVA
Secondary
German Revised Children's Quality of Life Questionnaire (KINDL-R): Physical Well-Being Score
KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the Physical Well-Being subscale is 0; highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Physical Well-Being Score | 69.1 units on a scale | Standard Error 2.7 |
| Atomoxetine Slow Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Physical Well-Being Score | 71.9 units on a scale | Standard Error 2.6 |
| Placebo | German Revised Children's Quality of Life Questionnaire (KINDL-R): Physical Well-Being Score | 78.1 units on a scale | Standard Error 2.6 |
p-value: 0.01795% CI: [-13.8, -1.4]ANCOVA
Secondary
German Revised Children's Quality of Life Questionnaire (KINDL-R): School Score
KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the School subscore is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): School Score | 63.4 units on a scale | Standard Error 2.8 |
| Atomoxetine Slow Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): School Score | 67.4 units on a scale | Standard Error 2.8 |
| Placebo | German Revised Children's Quality of Life Questionnaire (KINDL-R): School Score | 60.5 units on a scale | Standard Error 2.8 |
p-value: 0.13895% CI: [-1.6, 11.5]ANCOVA
Secondary
German Revised Children's Quality of Life Questionnaire (KINDL-R): Self Esteem Score
KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the Self Esteem subscale is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Self Esteem Score | 60.1 units on a scale | Standard Error 2.5 |
| Atomoxetine Slow Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Self Esteem Score | 57.3 units on a scale | Standard Error 2.4 |
| Placebo | German Revised Children's Quality of Life Questionnaire (KINDL-R): Self Esteem Score | 48.0 units on a scale | Standard Error 2.4 |
p-value: <0.00195% CI: [4.9, 16.4]ANCOVA
Secondary
German Revised Children's Quality of Life Questionnaire (KINDL-R): Total Quality of Life Score
KINDL-R (Revidierter KINDer Lebensqualitatsfragebogen, revised version), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score in the Total QOL score is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher score indicates better QOL.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Total Quality of Life Score | 66.0 units on a scale | Standard Error 1.8 |
| Atomoxetine Slow Titration | German Revised Children's Quality of Life Questionnaire (KINDL-R): Total Quality of Life Score | 65.6 units on a scale | Standard Error 1.8 |
| Placebo | German Revised Children's Quality of Life Questionnaire (KINDL-R): Total Quality of Life Score | 60.7 units on a scale | Standard Error 1.8 |
p-value: 0.02195% CI: [0.8, 9.3]ANCOVA
Secondary
Impact on Family Scale (FaBel), Total Impact Score
Family burden is assessed by the FaBel questionnaire (German version of the Impact on Family Scale). Questionnaire is answered by participant's caregiver and contains 33 Likert-scaled items to assess general negative impact (of a disability, disorder, disease) on parents, description of social relationships, concern for siblings, financial impact, problems in coping as well as a total score. Each item is rated on a 4-point scale (1=fully applies, 4=applies not at all). Total scores range from 24-96. Higher scores correspond to higher family burden.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Impact on Family Scale (FaBel), Total Impact Score | 54.2 units on a scale | Standard Error 1.4 |
| Atomoxetine Slow Titration | Impact on Family Scale (FaBel), Total Impact Score | 50.6 units on a scale | Standard Error 1.4 |
| Placebo | Impact on Family Scale (FaBel), Total Impact Score | 53.8 units on a scale | Standard Error 1.4 |
p-value: 0.40695% CI: [-4.9, 2]ANCOVA
Secondary
Investigator-Rated Individual Target Behaviors (ITB-Inv): Frequency Score
ITB-Inv assesses frequency and intensity of individually-defined target behaviors. The investigator defines 3 individual behavior problems based on interviews and additional information. Those most impairing for the child or stressful for the parents will be chosen as target behavior. Frequency of each target behavior during the last 7 days is rated on a 6-point scale (0=never to 5=always) with 0 as lowest possible score and 15 the highest possible score.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Investigator-Rated Individual Target Behaviors (ITB-Inv): Frequency Score | 6.0 units on a scale | Standard Error 0.6 |
| Atomoxetine Slow Titration | Investigator-Rated Individual Target Behaviors (ITB-Inv): Frequency Score | 6.6 units on a scale | Standard Error 0.6 |
| Placebo | Investigator-Rated Individual Target Behaviors (ITB-Inv): Frequency Score | 8.1 units on a scale | Standard Error 0.6 |
p-value: 0.0195% CI: [-3.2, -0.4]Mixed Models Analysis
Secondary
Investigator-Rated Individual Target Behaviors (ITB-Inv): Intensity Score
ITB-Inv assesses frequency and intensity of individually-defined target behaviors. The investigator defines 3 individual behavior problems based on interviews and additional information. Those most impairing for the child or stressful for the parents will be chosen as target behavior. Intensity during the last 7 days is rated on a 10-point scale (0=no problems to 9=most severe problems) with the lowest possible score of 0 and the highest possible of 27.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Investigator-Rated Individual Target Behaviors (ITB-Inv): Intensity Score | 10.8 units on a scale | Standard Error 1.1 |
| Atomoxetine Slow Titration | Investigator-Rated Individual Target Behaviors (ITB-Inv): Intensity Score | 11.9 units on a scale | Standard Error 1 |
| Placebo | Investigator-Rated Individual Target Behaviors (ITB-Inv): Intensity Score | 14.9 units on a scale | Standard Error 1.1 |
p-value: 0.0195% CI: [-6.2, -0.9]Mixed Models Analysis
Secondary
Number of Participants Discontinuing Treatment
Originally, time to treatment discontinuation was analyzed, deeming participants 'censored' if they reached the end of the observation period, were lost to followup, or withdrew informed consent. Because the median was not reached, the number of participants who discontinued (i.e., those who were not censored) is reported here.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine Fast Titration | Number of Participants Discontinuing Treatment | Age <12 Years | 4 participants |
| Atomoxetine Fast Titration | Number of Participants Discontinuing Treatment | Age >=12 Years | 2 participants |
| Atomoxetine Slow Titration | Number of Participants Discontinuing Treatment | Age <12 Years | 8 participants |
| Atomoxetine Slow Titration | Number of Participants Discontinuing Treatment | Age >=12 Years | 5 participants |
| Placebo | Number of Participants Discontinuing Treatment | Age <12 Years | 15 participants |
| Placebo | Number of Participants Discontinuing Treatment | Age >=12 Years | 4 participants |
p-value: 0.01695% CI: [1.16, 4.146]Log Rank
Secondary
Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment
Number of participants who experienced pre-specified categories of clinically relevant adverse events during the initial three-weeks of study treatment. NOTE: this is a subset of the overall adverse events which are reported by participant and event.
Time frame: 3 weeks
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine Fast Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Nausea or related symptoms | 21 participants |
| Atomoxetine Fast Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Fatigue or related symptoms | 19 participants |
| Atomoxetine Fast Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Gastrointestinal complaints | 12 participants |
| Atomoxetine Fast Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Sleep disturbances | 2 participants |
| Atomoxetine Slow Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Sleep disturbances | 2 participants |
| Atomoxetine Slow Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Nausea or related symptoms | 18 participants |
| Atomoxetine Slow Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Gastrointestinal complaints | 8 participants |
| Atomoxetine Slow Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Fatigue or related symptoms | 14 participants |
| Placebo | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Sleep disturbances | 1 participants |
| Placebo | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Fatigue or related symptoms | 6 participants |
| Placebo | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Gastrointestinal complaints | 2 participants |
| Placebo | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment | Nausea or related symptoms | 5 participants |
p-value: 0.102Fisher Exact
Secondary
Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period
Number of participants who experienced pre-specified categories of clinically relevant adverse events during the nine-week study treatment period. NOTE: this is a subset of the overall adverse events which are reported by participant and event.
Time frame: 9 weeks
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine Fast Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Nausea or related symptoms | 25 participants |
| Atomoxetine Fast Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Fatigue or related symptoms | 20 participants |
| Atomoxetine Fast Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Gastrointestinal complaints | 14 participants |
| Atomoxetine Fast Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Sleep disturbances | 4 participants |
| Atomoxetine Slow Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Sleep disturbances | 3 participants |
| Atomoxetine Slow Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Nausea or related symptoms | 21 participants |
| Atomoxetine Slow Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Gastrointestinal complaints | 12 participants |
| Atomoxetine Slow Titration | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Fatigue or related symptoms | 14 participants |
| Placebo | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Sleep disturbances | 2 participants |
| Placebo | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Fatigue or related symptoms | 6 participants |
| Placebo | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Gastrointestinal complaints | 3 participants |
| Placebo | Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period | Nausea or related symptoms | 6 participants |
p-value: 0.101Fisher Exact
Secondary
Parent-Rated Attention-Deficit Scale (FBB-HKS), Total Score: Severity
FBB-HKS (Fremdbeurteilungsbogen fur Hyperkinetische Storungen), the German, parent-rated scale for attention-deficit, is a 20-item rating scale which describes ADHD symptom criteria of DSM-IV and is grouped based upon the 3 ADHD domains: inattention (items 1-9); hyperactivity (items 10-16); impulsivity (items 17-20). Parents rated symptom severity of each item during the last 7 days on a 0 to 3 scale (0=not at all to 3=very much). The total score was calculated for ADHD overall (sum of ratings for items 1-20, divided by 20). Higher scores indicate higher severity of symptoms.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Parent-Rated Attention-Deficit Scale (FBB-HKS), Total Score: Severity | 1.2 units on a scale | Standard Error 0.1 |
| Atomoxetine Slow Titration | Parent-Rated Attention-Deficit Scale (FBB-HKS), Total Score: Severity | 1.1 units on a scale | Standard Error 0.1 |
| Placebo | Parent-Rated Attention-Deficit Scale (FBB-HKS), Total Score: Severity | 1.5 units on a scale | Standard Error 0.1 |
p-value: <0.00195% CI: [-0.6, -0.2]Mixed Models Analysis
Secondary
Parent-Rated Oppositional Defiant/Conduct Disorders Scale (FBB-SSV): Total Score, Severity
FBB-SSV (Fremdbeurteilungsbogen fur Storungen des Sozialverhaltens), the German, parent-rated oppositional defiant/conduct disorders scale, covers 23 criteria for ODD and 25 for conduct disorder (CD) in four sections. Parents rated symptom severity of each item during the last 7 days on a 0 to 3 scale (0=not at all to 3=very much). The total score was calculated for ODD/CD overall (sum of ratings for items 1-17, divided by 17). Higher scores indicate higher severity of symptoms.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Parent-Rated Oppositional Defiant/Conduct Disorders Scale (FBB-SSV): Total Score, Severity | 0.8 units on a scale | Standard Error 0.1 |
| Atomoxetine Slow Titration | Parent-Rated Oppositional Defiant/Conduct Disorders Scale (FBB-SSV): Total Score, Severity | 0.8 units on a scale | Standard Error 0.1 |
| Placebo | Parent-Rated Oppositional Defiant/Conduct Disorders Scale (FBB-SSV): Total Score, Severity | 1.0 units on a scale | Standard Error 0.1 |
p-value: 0.00695% CI: [-0.4, -0.1]Mixed Models Analysis
Secondary
Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Combined Score
The SNAP-IV: ADHD Combined Subscale for inattention (items 1-9) and hyperactivity/impulsivity (items 11-19) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 54.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Combined Score | 22.9 units on a scale | Standard Error 1.5 |
| Atomoxetine Slow Titration | Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Combined Score | 21.3 units on a scale | Standard Error 1.4 |
| Placebo | Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Combined Score | 29.6 units on a scale | Standard Error 1.5 |
p-value: <0.00195% CI: [-11, -3.8]Mixed Models Analysis
Secondary
Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Inattention Score
The SNAP-IV: ADHD Inattention Subscale (items 1-9) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 27.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Inattention Score | 11.1 units on a scale | Standard Error 0.7 |
| Atomoxetine Slow Titration | Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Inattention Score | 10.0 units on a scale | Standard Error 0.7 |
| Placebo | Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Inattention Score | 14.1 units on a scale | Standard Error 0.7 |
p-value: <0.00195% CI: [-5.3, -1.8]Mixed Models Analysis
Secondary
Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): Hyperactivity/Impulsivity Score
The SNAP-IV: ADHD Hyperactivity/Impulsivity Subscale (items 10-18) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 27.
Time frame: 9 weeks
Population: All participants randomized and receiving at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine Fast Titration | Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): Hyperactivity/Impulsivity Score | 11.5 units on a scale | Standard Error 0.8 |
| Atomoxetine Slow Titration | Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): Hyperactivity/Impulsivity Score | 11.1 units on a scale | Standard Error 0.7 |
| Placebo | Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): Hyperactivity/Impulsivity Score | 15.2 units on a scale | Standard Error 0.8 |
p-value: <0.00195% CI: [-5.8, -2]Mixed Models Analysis