An Italian Study of the Efficacy of Atomoxetine in the Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Comorbid Oppositional Defiant Disorder (ODD).

Study Overview
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Brief Summary
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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.

Official Title
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An Italian Randomised, Double-blind Placebo Controlled Study of the Efficacy of Atomoxetine Hydrochloride in the Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder and Comorbid Oppositional Defiant Disorder

Conditions
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Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder

Intervention / Treatment
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* Drug: atomoxetine 0.5 mg/kg/day
* Drug: placebo
* Drug: atomoxetine 1.2 mg/kg/day
* Drug: atomoxetine 1.2-1.4 mg/kg/day


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atomoxetine<br>atomoxetine 0.5 milligrams per kilogram per day (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 receives marketing approval. | Drug: atomoxetine 0.5 mg/kg/day<br>* atomoxetine 0.5 milligrams per kilogram per day (mg/kg/day) daily (QD), by mouth (PO)<br>* Other names: Strattera;Drug: atomoxetine 1.2 mg/kg/day<br>* atomoxetine 1.2 mg/kg/day QD, PO<br>* Other names: Strattera;Drug: atomoxetine 1.2-1.4 mg/kg/day<br>* atomoxetine 1.2 - 1.4 mg/kg/day QD, PO<br>* Other names: Strattera;|
| Placebo Comparator: Placebo<br>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 receives marketing approval. | Drug: atomoxetine 0.5 mg/kg/day<br>* atomoxetine 0.5 milligrams per kilogram per day (mg/kg/day) daily (QD), by mouth (PO)<br>* Other names: Strattera;Drug: placebo<br> <br> Drug: atomoxetine 1.2-1.4 mg/kg/day<br>* atomoxetine 1.2 - 1.4 mg/kg/day QD, PO<br>* Other names: Strattera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Visit 8 (baseline) and Visit 14 (8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Visit 8 (baseline) and Visit 14 (8 weeks) | 
| 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. | Visit 8 (baseline) and Visit 14 (8 weeks) | 
| 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. | Visit 8 (baseline) and Visit 14 (8 weeks) | 
| 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. | Visit 8 (baseline) and Visit 14 (8 weeks) | 
| 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. | Visit 8 (baseline) and Visit 14 (8 weeks) | 
| 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. | Visit 8 (baseline) and Visit 14 (8 weeks) | 
| 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. | Visit 8 (baseline) and Visit 14 (8 weeks) |