Efficacy and Safety of Atomoxetine in Children With Recent Diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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Double blinded clinical trial placebo controlled in 153 children (planned enrollment) with recent diagnosis of ADHD. Patients will be randomized to atomoxetine or placebo arm (2:1). The double blinded period will last 12 weeks and the treatment open phase will last up to 1 year, and atomoxetine treatment will be administered. A gatekeeper strategy will be employed for sequentially testing the secondary objectives.

Official Title
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A Randomized Double-Blind, Placebo-Controlled Clinical Trial of Efficacy and Safety of Atomoxetine up to 12 Weeks in Newly Diagnosed Children and Adolescents Outpatients With Attention-Deficit/Hyperactivity Disorder

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Atomoxetine Hydrochloride
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Child or adolescent patients must be at least 6 years of age, but must not yet have reached their 16th birthday prior to Visit 1, when informed consent is obtained. Patients must meet the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) diagnostic criteria for ADHD. For the purposes of this study the diagnosis of ADHD will be confirmed during Visit 1 by administering the K-SADS-PL. Patients must also have an ADHDRS-IV-Parent:Inv score at least 1.5 standard deviations above the age norm for their diagnostic subtype at both Visit 1 and Visit 2. In addition, they must have a CGI-ADHD-S score 4 at both Visit 1 and Visit 2. Patients must have a newly diagnosed case of ADHD. Newly diagnosed case of ADHD means that a specialist (including pediatrician, child psychiatrist, or child neurologist) or child psychologist has diagnosed ADHD (according DSM-IV-TR or International Statistical Classification of Diseases and Related Health Problems [World Health Organisation; 10th Revision] [ICD 10] criteria) within 3 months prior to Visit 1. Exclusion Criteria: Patients with history of ADHD diagnosis longer than 3 months prior to Visit 1. Diagnosis of ADHD means that a specialist (including pediatrician, child psychiatrist, or child neurologist) or child psychologist has diagnosed ADHD (according DSM-IV-TR or ICD 10 criteria) and has registered it in medical records or verbally informed parents about this diagnosis. Patients who weigh less than 20 kg at study entry (Visit 1). If a patient's weight changes after Visit 1 to a value outside of the stated range, the patient will still be eligible, and the weight should be rounded to the nearest value within the above range for dosing purposes.

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 mg/kg/day every day (QD),by mouth (PO) for 2 weeks, 1.2 - 1.4 mg/kg/day QD, PO for 10 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1 year | Drug: Atomoxetine Hydrochloride<br> <br> * Other names: Strattera;|
| Placebo Comparator: Placebo<br>placebo every day (QD), by mouth (PO) for 12 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 year (open-label extension) | Drug: Atomoxetine Hydrochloride<br> <br> * Other names: Strattera;Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 12 Week Endpoint | Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total Scores range from 0 to 54. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 9 Weeks | Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. | Week 9 | 
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 6 Weeks | Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. | Week 6 | 
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score at 4 Weeks | Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. | Week 4 | 
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score Change From Week 6 to Week 12 | Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. | week 6 and week 12 | 
| Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Changes From Baseline to Visit 7 (12 Weeks) | Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients). | Baseline and 12 weeks | 
| Clinical Global Impressions- Attention-Deficit/Hyperactivity Disorder-Severity Change From Baseline to Endpoint (Visit 18) of the Open-Label Extension (107 Weeks) | Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients). | Baseline and Open-Label Endpoint (107 weeks) | 
| Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Total Score Changes From Baseline to Endpoint (Week 12) | The CPRS-R:S has 27 items to be completed by the parent to assess behavioral problems related to ADHD. Individual item scores range from 0 (not at all true/never/seldom: lowest impairment) to 3 (very much true/very often/very frequent: highest impairment). The total score is calculated as the sum of all items. Total scores range from 0 to 81. | Baseline and Week 12 | 
| Child Health and Illness Profile (CHIP) Change From Baseline to Endpoint (12 Weeks) | Parent-rated assessment of a child's health status and level of functioning. It consists of 76 items. The majority of items assess frequency of activities or feelings using a five-point response format (for example, 'how good is your child at making friends?' 1=never, 5=always). Standard scores (t-value) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Standard scores are expressed in standard deviation units. T-score=[(Score-4.2382)*10/0.32835]+50. Higher scores mean improvement. | Baseline to 12 weeks | 
| Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) | The K-SADS-PL is a semi-structured interview schedule for assessing psychiatric disorders in children and adolescents. It is used to assess the status of 32 DSM-IV child and adolescent psychiatric diagnosis. | Baseline | 
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) at 107 Weeks (Open-Label Extension) | Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. | Week 107 | 
| Vital Signs - Systolic Blood Pressure |  | Baseline and 12 weeks | 
| Vital Signs - Diastolic Blood Pressure |  | Baseline and 12 weeks | 
| Vital Signs - Pulse |  | Baseline and 12 weeks | 
| Vital Signs - Weight |  | Baseline and 12 weeks |