A Study Comparing the Effect of Atomoxetine Versus Other Standard Care Therapy on the Long Term Functioning in Attention-Deficit/Hyperactivity Disorder (ADHD) Children and Adolescents

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that atomoxetine is superior to other early standard therapy (any treatment that investigator considers is appropriate to initiate for the treatment of Attention-Deficit/Hyperactivity Disorder [ADHD]) on the long term functioning in approximately 400 children and adolescents with ADHD. Patients will be pharmacological naïve prior to entry into the study.

Official Title
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A Randomized, Controlled, Open-Label Study of the Long-Term Impact on Functioning Using Atomoxetine Hydrochloride Compared to Other Early Standard Care in the Treatment of Attention-Deficit/Hyperactivity Disorder in Treatment-Naïve Children and Adolescents

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Atomoxetine
* Drug: Other standard therapy for ADHD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria: 6 to 16 years old Diagnosis of ADHD according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV) confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (SADS PL) Pharmacological naïve Normal intelligence as assessed by investigator Each patient (and/or legally authorized patient representative where required by local law) must understand the nature of the study and must sign an Informed Consent Document. Exclusion Criteria: Exclusion criteria History of bipolar disorder, any history of psychosis or autism spectrum disorder History of any seizure disorder Significant prior or current medical conditions History of alcohol or drug abuse within the past 3 months Patients who are taking concurrently any of the excluded medications in the study.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 16 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atomoxetine<br>0.5 mg/kg/day once a day (QD) or twice a day (BID) for 1 week then 1.2-1.8 mg/kg/day QD or BID for 6 months, up to an additional 6 months optional extension | Drug: Atomoxetine<br>* 0.5 mg/kg/day once a day (QD) or twice a day (BID) for 1 week then 1.2-1.8 mg/kg/day QD or BID for 6 months, up to an additional 6 months optional extension<br>* Other names: Strattera;|
| Active Comparator: OEST<br>Other Early Standard Treatment (OEST): any treatment for ADHD as prescribed by investigator, 6 months, up to an additional 6 months extension | Drug: Other standard therapy for ADHD<br>* Any treatment for ADHD as prescribed by investigator, 6 months, up to an additional 6 months extension<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 6 Month Endpoint in Child Health and Illness Profile - Child Edition, Parent Report Form (CHIP-CE PRF), Achievement Domain | CHIP-CE PRF: parent rated assessment of a child's health status/level of functioning. The achievement domain describes developmentally appropriate role functioning in school and with peers. The majority of items assess frequency of activities or feelings using a 5-point response format (1=never, 5=always). Standard scores (T-scores) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Normative range is 40 to 60. Higher scores indicate better health and lower scores indicate worse health. | Baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 4 Month and 12 Month Endpoints in CHIP-CE PRF, Achievement Domain | CHIP-CE PRF: parent rated assessment of a child's health status/level of functioning. The achievement domain describes developmentally appropriate role functioning in school and with peers. The majority of items assess frequency of activities or feelings using a 5-point response format (1=never, 5=always). Standard scores (T-scores) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Normative range is 40 to 60. Higher scores indicate better health and lower scores indicate worse health. | Baseline, 4 months, 12 months | 
| Change From Baseline to 4 Month, 6 Month, and 12 Month Endpoints in the CHIP-CE PRF Domain Scores (Satisfaction, Comfort, Resilience and Risk Avoidance) | CHIP-CE PRF: parent rated assessment of a child's health status and level of functioning. Domains: Satisfaction, Comfort, Risk Avoidance, Resilience. The majority of items assess frequency of activities or feelings using a 5-point response format (1=never, 5=always). Standard scores (T-scores) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Normative range is 40 to 60. Higher scores indicate better health and lower scores indicate worse health. | Baseline, 4 months, 6 months, 12 months | 
| Change From Baseline to 4 Month, 6 Month, and 12 Month Endpoints in Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) | The 50-item WFIRS-P rates impairment in 6 domains of functioning: home, school, self-concept, social, activities of daily living, and risk taking. Each item is rated by the parent on a 4-point Likert scale from 0 to 3 (0=never or not at all, 1=sometimes or somewhat, 2=often or much, 3=very often or very much). Average of non-missing values were calculated for each domain as well as the Total, which combined all 6 domains; therefore each scale including total has a range of 0 (best) to 3 (worst). | Baseline, 4 months, 6 months, 12 months | 
| Change From Baseline to 4 Month, 6 Month, and 12 Month Endpoints in Attention-Deficit/Hyperactivity Disorder Rating Scale - Parent Version: Investigator Adminitered and Scored (ADHD-RS-IV Parent:Inv) | Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) 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. Inattention and Hyperactivity-Impulsivity subscales consisted of 9 items each, for total subcale scores ranging from 0 to 27. Higher scores are indicative of more severe symptoms. | Baseline, 4 months, 6 months, 12 months | 
| Change From Baseline to 4 Month, 6 Month, and 12 Month Endpoints in Clinical Global Impression Attention-Deficit/Hyperactivity Disorder - Severity (CGI-ADHD-S) | 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, 4 months, 6 months, 12 months | 
| Change From Baseline to 4 Month, 6 Month, and 12 Month Endpoints in the CHIP-CE CRF for Children (6-11 Years) | CHIP-CE CRF: child rated assessment of their health status and level of functioning. Domains: Achievement, Satisfaction, Comfort, Risk Avoidance, Resilience. The majority of items assess frequency of activities or feelings using a 5-point response format (1=never, 5=always). Standard scores (T-scores) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Normative range is 40 to 60. Higher scores indicate better health and lower scores indicate worse health. | Baseline, 4 months, 6 months, 12 months | 
| Change From Baseline to 4 Month, 6 Month, and 12 Month Endpoints in the CHIP-Adolescent Edition (AE) for Adolescents (>11-17 Years) | CHIP-AE CRF: adolescent rated assessment of their health status and level of functioning. Domains: Achievement, Satisfaction, Comfort, Risk Avoidance, Resilience. The majority of items assess frequency of activities or feelings using a 5-point response format (1=never, 5=always). Standard scores (T-scores) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Normative range is 40 to 60. Higher scores indicate better health and lower scores indicate worse health. | Baseline, 4 months, 6 months, 12 months | 
| Correlation Between CHIP-CE Parent Rated and Pooled CHIP-CE Child Rated and CHIP AE Adolescent Rated T-Scores | Pearson correlation coefficients were calculated on each domain at baseline, Month 6 and Change to Month 6 between parent-rated CHIP and pooled patient-rated (child and adolescent) CHIP. | Baseline, 6 months |