Comparison of Lisdexamfetamine Dimesylate With Atomoxetine HCl in Attention-Deficit/Hyperactivity Disorder (ADHD) Subjects With an Inadequate Response to Methylphenidate

Study Overview
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Brief Summary
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This study will evaluate how long it takes for ADHD symptoms to improve in subjects who are judged by the Investigator to have had an inadequate response to methylphenidate therapy. The study will also test the safety of Lisdexamfetamine Dimesylate and how well it works.

Official Title
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A Phase 3b, Double-blind, Randomised, Active-controlled, Parallel Group Study to Assess the Time to Response of Lisdexamfetamine Dimesylate to Atomoxetine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hyperactivity Disorder (ADHD) Who Have Had an Inadequate Response to Methylphenidate Therapy

Conditions
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Attention-Deficit/Hyperactivity Disorder

Intervention / Treatment
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* Drug: Lisdexamfetamine Dimesylate
* Drug: Atomoxetine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has had an historical or current inadequate response to methylphenidate (MPH) treatment. Inadequate response includes but is not limited to the presence of some residual symptoms, with associated impairment inadequate duration of action and/or variability of symptom control, and/or Investigator feels that the subject may derive benefit from an alternative drug treatment to MPH therapy. Subject is a male or female aged 6-17 years inclusive at the time of consent Subject must meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition. - Text Revision (DSM IV TR) criteria for a primary diagnosis of ADHD based on a detailed psychiatric evaluation Subject must have a baseline ADHD-RS-IV total score 28. Exclusion Criteria: Subject has taken more than 1 MPH treatment (for example, 2 or more different MPH treatments). Examples include but are not limited to RITALIN immediate release (IR) and EQUASYM IR; MEDIKINET IR and CONCERTA; RITALIN long-acting LA and CONCERTA. Note: this does not include subjects who have taken IR MPH for dose titration on a short-term basis (for example, £4 weeks) with an adequate response In the Investigator's judgement, subject has failed to respond to more than 1 previous course(s) of MPH treatment. Failure to respond includes worsening of symptoms or no change/minimal improvement of symptoms. Subject has previously been exposed to STRATTERA or to amphetamine therapy Subject has previously demonstrated intolerable side effects to 1 MPH treatment which limited titration to acceptable efficacy or that required a decrease in dose resulting in unacceptable tolerability and/or efficacy Subject has a current, controlled (requiring a restricted medication) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as any severe comorbid Axis II disorder or severe Axis I disorder or other symptomatic manifestations, such as agitated states, marked anxiety, or tension that, in the opinion of the examining physician, will contraindicate treatment with SPD489 or STRATTERA or confound efficacy or safety assessments. Subject has a conduct disorder. Oppositional Defiant Disorder is not exclusionary.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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: Lisdexamfetamine Dimesylate<br> | Drug: Lisdexamfetamine Dimesylate<br>* Oral 30, 50, or 70mg once-daily for 9 weeks<br>* Other names: Vyvanse;|
| Active Comparator: Atomoxetine Hydrochloride<br> | Drug: Atomoxetine Hydrochloride<br>* Oral 10mg to 100mg once-daily for 9 weeks<br>* Other names: Strattera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Response | Time to first response was defined as a Clinical Global Impression-Improvement (CGI-I) value of 1 (very much improved) or 2 (much improved) first recorded following first dose of investigational product. CGI-I consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores - Last Observation Carried Forward (LOCF) | Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. | 9 weeks | 
| Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at 9 Weeks - LOCF | ADHD-RS-IV consists of 18 items scored on a 4-point scale from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. A decrease in score indicates an improvement in ADHD symptomology. | Baseline and 9 weeks | 
| Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Up to 9 Weeks | The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment. | Baseline and up to 9 weeks | 
| Health Utilities Index-2 (HUI-2) Scores at Up to 9 Weeks | HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status. | up to 9 weeks | 
| Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Up to 9 Weeks | The BPRS-C characterizes psychopathology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology. | Baseline and up to 9 weeks | 
| Columbia-Suicide Severity Rating Scale (C-SSRS) | C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale. | 9 weeks | 
| Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 | UKU-SERS-Clin is composed of 48 items each of which asks about a single side effect. Each side effect is rated based on a 4-point scale ranging from 0 (no or doubtful presence) to 3 (the least favorable rating). The rating is independent of whether the symptom is regarded as related to the investigational product. | 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD