Comparison of Slow and Fast Transition From Stimulants to Atomoxetine in Children and Adolescents With Attention Deficit/Hyperactivity Disorder(ADHD)

Study Overview
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Brief Summary
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Children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) who are not tolerating or not responding well to stimulant therapy will be included in this study. Two different strategies for transition from Stimulant to Atomoxetine will be used: Slow (10 weeks) and fast (2 weeks). Changes in ADHD symptoms and tolerability of medication will be compared between the two different switching approaches.

Detailed Description
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Study B4Z-EW-LYFJ is a phase IV multicentre, open label, controlled study in approximately 120 patients with ADHD from 6 years to 16 years of age. After the screening period, patients will be randomized (centrally in a 1:1 ratio) either to a transition period of 10 weeks (slow switching arm) or to a transition period of 2 weeks (fast switching arm). After completion of the 10 week open phase patients will be treated for a further 4 weeks with atomoxetine.

Official Title
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A Randomized, Controlled, Open-Label Comparison Study of the Efficacy and Safety of Slow Transitioning Compared With Fast Transitioning From a Stimulant Medication to Atomoxetine in Pediatric and Adolescent Outpatients With DSM-IV Attention-Deficit/Hyperactivity Disorder (ADHD)

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Atomoxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients between 6-16 years of age Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnostic criteria for ADHD must be met Normal laboratory and electrocardiogram (ECG) results Normal intelligence Must have unsatisfactory symptom response to stimulant therapy or experience of adverse events while on stimulant therapy Exclusion Criteria: Less than 20 kg or more than 70 kg at study entry Concomitant major psychiatry disorders, drug or alcohol abuse or serious suicide risk Medical conditions such as seizures, severe allergies, glaucoma, cardiovascular disease, hypertension, or acute or unstable medical conditions Taking of anticonvulsants, antihypertensive agents, medication with sympathomimetic activity, psychotropic medications, monoamine oxidase inhibitor Immediate need for stimulant discontinuation due to tolerability problems Previous participation in an atomoxetine study, or unresponsive to atomoxetine, or intolerable side effects to atomoxetine

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: Slow Switching Group<br>Slow Switching Group (switch from full stimulant dose to atomoxetine, 1.2 mg/kg/day, orally (PO), during 10 weeks then continue treatment up to 1.8 mg/kg/day, PO to 14 weeks | Drug: Atomoxetine<br>* 1.2 mg/kg/day up to 1.8 mg/kg/day, orally (PO)<br>* Other names: Strattera;|
| Experimental: Fast Switching Group<br>Fast Switching Group (switch from full stimulant dose to atomoxetine 1.2 mg/kg/day, PO, during 2 weeks then continue treatment up to 1.8 mg/kg/day, PO to 14 weeks | Drug: Atomoxetine<br>* 1.2 mg/kg/day up to 1.8 mg/kg/day, orally (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 in Attention Deficit Hyperactivity Disorder-Rating Scale (ADHD-RS-IV) Parent Version: Investigator Administered and Scored - Total Score at Week 10 Endpoint | 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 (ADHD). Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. Higher score indicates greater severity of disease. Least squares means are adjusted for baseline, site, treatment, visit and treatment by visit interaction. | Baseline, 10 weeks | 
| Change From Baseline in ADHD-RS-IV Parent Version: Investigator Administered and Scored - Total Score at Week 2 Endpoint | Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of ADHD. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. Higher score indicates greater severity of disease. Least squares means are adjusted for baseline, site, treatment, visit and treatment by visit interaction. | Baseline, 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Global Impression of Perceived Difficulties (GIPD) Rating Scale - Patient Total Score at Week 10 Endpoint | The GIPD scale is a 5-item rating of ADHD-related difficulties (overall difficulties perceived in the morning, during school, during homework, in the evening, and over the entire day and night). For each item, difficulties during the past week are rated on a 7-point scale (1 = normal, not difficult at all; 7 = extremely difficult) and the mean of the 5 items is reported. Least square means are adjusted for baseline, site, treatment, visit and treatment by visit interaction. | Baseline, 10 weeks | 
| Change From Baseline in Global Impression of Perceived Difficulties (GIPD) Rating Scale- Parent Total Score at Week 10 Endpoint | The GIPD scale is a 5-item rating of ADHD-related difficulties (overall difficulties perceived in the morning, during school, during homework, in the evening, and over the entire day and night). For each item, difficulties during the past week are rated on a 7-point scale (1 = normal, not difficult at all; 7 = extremely difficult) and the mean of the 5 items is reported. Least square means are adjusted for baseline, site, treatment, visit and treatment by visit interaction. | Baseline, 10 weeks | 
| Change From Baseline in Global Impression of Perceived Difficulties (GIPD) Rating Scale- Investigator Total Score at Week 10 Endpoint | The GIPD scale is a 5-item rating of ADHD-related difficulties (overall difficulties perceived in the morning, during school, during homework, in the evening, and over the entire day and night). For each item, difficulties during the past week are rated on a 7-point scale (1 = normal, not difficult at all; 7 = extremely difficult) and the mean of the 5 items is reported. Least square means are adjusted for baseline, site, treatment, visit and treatment by visit interaction. | Baseline, 10 weeks | 
| Change From Baseline in Clinical Global Impression Severity (CGI-S) Rating Scale - Total Score at Week 10 Endpoint | The CGI- S is a single-item clinician rating of the severity of the participant's ADHD symptoms in relation to the clinician's total experience of ADHD participants. Severity is rated on a seven-point scale (1 = normal, not ill at all; 7 = among the most extremely ill patients). Least square means are adjusted for baseline, site, treatment, visit and treatment by visit interaction. | Baseline, 10 weeks | 
| Change From Baseline in Child Health and Illness Profile Child Edition-Parent Report Form (CHIP-CE-PRF) - Domain Scores at Week 10 Endpoint | CHIP-CE-PRF consists of 76 items. The majority of items assess frequency of activities or feelings using a five-point response format. Standard scores (t-value) were established, with all domains and subdomains having a mean score of 50 and standard deviation (SD) of 10. Standard scores are expressed in SD units. T-score=[(Score- Mean for the reference population [Ref Pop])*10/SD for the Ref Pop]+50. Higher scores mean better quality of life. Least square means are adjusted for baseline, site, treatment, visit and treatment by visit interaction. | Baseline, 10 weeks | 
| Change From Baseline in Treatment Satisfaction Preference Survey Mean Score at Week 10 Endpoint | The Treatment Satisfaction Survey consists of a five-question survey each rated on a 5 point scale (0=very satisfied/very likely, 4=very dissatisfied/not at all likely). The mean score over the items is reported. | Baseline, 10 weeks | 
| Change From Baseline in Blood Pressure (BP) at Week 6 and Week 14 Endpoint |  | Baseline, 6 weeks, 14 weeks | 
| Change From Baseline in Pulse Rate at Week 6 and Week 14 Endpoint |  | Baseline, 6 weeks, 14 weeks | 
| Change From Baseline in Body Weight at Week 6 and Week 14 Endpoint |  | Baseline, 6 weeks, 14 weeks | 
| Number of Participants With Suicidal Behaviors and Ideations | Columbia Suicide Rating Scale (C-SSRS): scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors and ideations are provided. Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a yes answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. | Baseline through 14 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, Children, Stimulant, Atomoxetine, Adolescents