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

Attention Deficit Hyperactivity Disorder Clinical Trial

— ADHD SWITCH  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00760747
• Other study ID #: 12305
• Secondary ID: B4Z-EW-LYFJ
• Status: Completed
• Phase: Phase 4
• First received: September 25, 2008
• Last updated: August 2, 2011
• Start date: September 2008
• Est. completion date: September 2010

Study information

• Verified date: August 2011
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: September 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 16 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder
• Hyperkinesis

Intervention

Drug:
• Atomoxetine
1.2 mg/kg/day up to 1.8 mg/kg/day, orally (PO)

Locations

Country	Name	City	State
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Milton	Queensland
Mexico	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Zona Centro
United Kingdom	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Birmingham	West Midlands
United Kingdom	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fife	Scotland
United Kingdom	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Northampton
United Kingdom	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sheffield	South Yorkshire

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

Australia,  Mexico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Change From Baseline in Blood Pressure (BP) at Week 6 and Week 14 Endpoint		Baseline, 6 weeks, 14 weeks	Yes
Secondary	Change From Baseline in Pulse Rate at Week 6 and Week 14 Endpoint		Baseline, 6 weeks, 14 weeks	Yes
Secondary	Change From Baseline in Body Weight at Week 6 and Week 14 Endpoint		Baseline, 6 weeks, 14 weeks	Yes
Secondary	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	Yes