Efficacy of Atomoxetine on Psychosocial Function of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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This study aims to assess the effectiveness of atomoxetine on psychosocial functioning and emotional well being of children and adolescents with ADHD and to evaluate whether and in what measure the presence of comorbid conditions (internalizing and externalizing disorders) influences atomoxetine's ability to improve the quality of life of ADHD subjects.

Official Title
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An Open-Label Study of the Efficacy of Atomoxetine Hydrochloride on Quality of Life of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder With or Without Comorbid Conditions

Conditions
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Attention Deficit Disorder With Hyperactivity

Intervention / Treatment
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* Drug: atomoxetine


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 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 Subscale (SNAP-IV ADHD Subscale) score at both Visit 1 and 2 Laboratory results, including serum chemistries, hematology, and urinalysis, must show no clinically significant abnormalities (clinically significant is defined as laboratory values requiring acute medical intervention, indicating a serious medical illness, or requiring further medical evaluation in the judgment of the investigator) An electrocardiogram (ECG) must be performed to exclude cardiac diseases at the baseline/screening visit and the results must be reviewed by the investigator at Visit 2 prior to dispensing of study material Patients and parents have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests, including venipuncture, and examinations required by the protocol. Exclusion Criteria: 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 with significant cardiovascular disease or other conditions that could be aggravated by an increased heart rate or increased blood pressure Patients who have any medical condition that would increase sympathetic nervous system activity markedly (for example, catecholamine-secreting neural tumor), or who are taking a medication on a daily basis (for example, albuterol, inhalation aerosols, pseudoephedrine), that has sympathomimetic activity. Such medications can be taken on an as-needed basis

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pure ADHD<br>Attention-Deficit/Hyperactivity Disorder (ADHD) alone. Received atomoxetine: 0.5 milligrams per kilogram per day (mg/kg/day), by mouth (PO) for 1 week then 1.2 mg/kg/day, PO for 11 weeks followed by up to 1.4 mg/kg/day, PO for up to 12 additional weeks | Drug: atomoxetine<br>* 0.5 milligrams per kilogram per day (mg/kg/day), by mouth (PO) for 1 week then 1.2 mg/kg/day, PO for 11 weeks followed by up to 1.4 mg/kg/day, PO for up to 12 additional weeks<br>* Other names: Strattera;|
| Experimental: ADHD+Internalizing Disorders<br>Attention-Deficit/Hyperactivity Disorder (ADHD) plus internalizing disorders. Received atomoxetine: 0.5 milligrams per kilogram per day (mg/kg/day), by mouth (PO) for 1 week then 1.2 mg/kg/day, PO for 11 weeks followed by up to 1.4 mg/kg/day, PO for up to 12 additional weeks | Drug: atomoxetine<br>* 0.5 milligrams per kilogram per day (mg/kg/day), by mouth (PO) for 1 week then 1.2 mg/kg/day, PO for 11 weeks followed by up to 1.4 mg/kg/day, PO for up to 12 additional weeks<br>* Other names: Strattera;|
| Experimental: ADHD+Externalizing Disorders<br>Attention-Deficit/Hyperactivity Disorder (ADHD) plus externalizing disorders. Received atomoxetine: 0.5 milligrams per kilogram per day (mg/kg/day), by mouth (PO) for 1 week then 1.2 mg/kg/day, PO for 11 weeks followed by up to 1.4 mg/kg/day, PO for up to 12 additional weeks | Drug: atomoxetine<br>* 0.5 milligrams per kilogram per day (mg/kg/day), by mouth (PO) for 1 week then 1.2 mg/kg/day, PO for 11 weeks followed by up to 1.4 mg/kg/day, PO for up to 12 additional weeks<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 12 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE), Achievement Domain | 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. Achievement Domain Range = -3.1 to 67.7. Higher scores mean greater health or level of functioning in achievement. | Baseline, 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 12 Week Endpoint in the Attention-Deficit/Hyperactivity Disorder (ADHD) Subscales of 18-Item Swanson, Nolan and Pelham Rating Scale (SNAP-IV) | 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: total score=0-27) and hyperactivity/impulsivity (items #11-#19: total score=0-27). The SNAP-IV is based on a 0 (not at all) to 3 (very much) rating scale. Total combined type (inattention plus hyperactivity/impulsivity) subscale scores range from 0 to 54. | Baseline, 12 Weeks | 
| Change From Baseline to 12 Week Endpoint in Clinical Global Impressions-ADHD-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, 12 Weeks | 
| Change From Baseline to 12 Week Endpoint in CHIP-CE Satisfaction, Comfort, Resilience and Risk Avoidance Domains | 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 having a mean score of 50 and standard deviation of 10. Satisfaction range=-25.7 to 66.3; Comfort=-28.6 to 67.2; Resilience=-36.3 to 71.8; Risk Avoidance=-23.5 to 62.5. Higher scores mean greater health or level of functioning in that domain. | Baseline, 12 Weeks | 
| Change From Baseline to 12 Week Endpoint in Pediatric Anxiety Rating Scale (PARS) | The Pediatric Anxiety Rating Scale (PARS) is used to rate the severity of anxiety in children and adolescents, ages 6 to 17 years. The total score for the PARS is derived by summing 5 of the 7 severity/impairment/interference items (2,3,5,6,7). The total score ranges from 0 (none) to 25 (extreme severity). Items 1 (overall number of anxiety symptoms) and 4 (overall severity of physical symptoms) are not included in the total score calculation. | Baseline, 12 Weeks | 
| Change From Baseline to 12 Week Endpoint in Children's Depression Rating Scale-Revised (CDRS-R) | 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. | Baseline, 12 Weeks | 
| Change From Baseline to 12 Week Endpoint in SNAP-IV Oppositional Scale | Items are included from the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for Oppositional Defiant Disorder. 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. | Baseline, 12 Weeks | 
| Change From Baseline to 12 Week Endpoint in Adolescent Symptom Inventory-4: Parent Checklist (ASI-4) | Parent-completed ASI-4 contains 120 items on 18 emotional and behavioral disorders in adolescents (12-18 years old). Item score range:0 (no symptoms) to 3 (maximum impairment). Categories: A=ADHD (0-54); B=Conduct (0-60); C=Oppositional Defiant (0-24); D=Generalized Anxiety (0-18); E=Specific Phobia/Panic Attack/Obsessions/Compulsions/Somatization (0-30); F=Social Phobia (0-6); G=Separation Anxiety (0-24); H=Schizoid Personality (0-9); I=Schizophrenia (0-6); J=Enuresis (0-18); K=Major Depressive (0-42); L=Bipolar (0-27); M=Anorexia (0-12); N=Bulimia (0-12); O=Substance Abuse (0-18). | Baseline, 12 Weeks | 
| Change From Baseline to 12 Week Endpoint in Child Symptom Inventory-4: Parent Checklist (CSI-4) | The CSI-4 contains 97 items that screen for 15 emotional and behavioral disorders in children between 5 and 12 years old. Item score range:0 (no symptoms) to 3 (maximum impairment). Categories: A=ADHD (0-54); B=Conduct (0-60); C=Oppositional Defiant (0-24); D=Generalized Anxiety (0-18); E=Specific Phobia/Panic Attack/Obsessions/Compulsions/Somatization (0-30); F=Social Phobia (0-6); G=Separation Anxiety (0-24); H=Schizoid Personality (0-9); I=Schizophrenia (0-6); J=Enuresis (0-18). | Baseline, 12 Weeks | 
| Change From Baseline to 12 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form (CTRS-R:S) | 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. | Baseline, 12 Weeks |