Comparison of Atomoxetine Versus Placebo in Children and Adolescents With ADHD and Comorbid ODD in Germany

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00406354
First received: November 29, 2006
Last updated: February 19, 2010
Last verified: February 2010
  Purpose

A three-arm, randomized, double-blind, placebo-controlled, Phase 4, multicenter study to compare the efficacy and safety of atomoxetine versus placebo in children and adolescents aged 6 through 17 years with attention-deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) who are treated as outpatients in Germany. After an initial 3- to 28-day screening and washout phase, participants will be assigned to double-blind treatment with atomoxetine or placebo. A 2 week up-titration period will be succeeded by a 7 week treatment period at the target dose. The primary efficacy measure will be the Swanson, Nolan and Pelham Rating Scale Revised (SNAP-IV) ODD subscale score.


Condition Intervention Phase
Attention Deficit Hyperactivity Disorder
Oppositional Defiant Disorder
Drug: Atomoxetine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind Comparison of Atomoxetine Versus Placebo in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder and Comorbid Oppositional Defiant Disorder

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Swanson, Nolan and Pelham Rating Scale Revised (SNAP-IV) Oppositional Defiant Disorder: (ODD) Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The SNAP-IV, a 26-item scale, includes 1 item for each of the 18 symptoms contained in the DSM-IV diagnosis of ADHD and 1 item for each of the 8 symptoms contained in the DSM-IV diagnosis of ODD. Each item is scored on a 0 to 3 scale (0=Not at All, 1=Just a Little, 2=Pretty Much, 3=Very Much). The SNAP-IV yields scores in three domains: Inattention (items 1-9: subscore range=0-27), Hyperact-ivity/Impulsivity (items 10-18: subscale range=0-27), and Oppositional (items 19-26: subscale range=0-24). SNAP-IV: ADHD Combined Scale score (inattention + hyperactivity/impulsivity) ranges from 0-54.


Secondary Outcome Measures:
  • Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Combined Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The SNAP-IV: ADHD Combined Subscale for inattention (items 1-9) and hyperactivity/impulsivity (items 11-19) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 54.

  • Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Inattention Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The SNAP-IV: ADHD Inattention Subscale (items 1-9) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 27.

  • Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): Hyperactivity/Impulsivity Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The SNAP-IV: ADHD Hyperactivity/Impulsivity Subscale (items 10-18) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 27.

  • Parent-Rated Attention-Deficit Scale (FBB-HKS), Total Score: Severity [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    FBB-HKS ("Fremdbeurteilungsbogen fur Hyperkinetische Storungen"), the German, parent-rated scale for attention-deficit, is a 20-item rating scale which describes ADHD symptom criteria of DSM-IV and is grouped based upon the 3 ADHD domains: inattention (items 1-9); hyperactivity (items 10-16); impulsivity (items 17-20). Parents rated symptom severity of each item during the last 7 days on a 0 to 3 scale (0=not at all to 3=very much). The total score was calculated for ADHD overall (sum of ratings for items 1-20, divided by 20). Higher scores indicate higher severity of symptoms.

  • Parent-Rated Oppositional Defiant/Conduct Disorders Scale (FBB-SSV): Total Score, Severity [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    FBB-SSV ("Fremdbeurteilungsbogen fur Storungen des Sozialverhaltens"), the German, parent-rated oppositional defiant/conduct disorders scale, covers 23 criteria for ODD and 25 for conduct disorder (CD) in four sections. Parents rated symptom severity of each item during the last 7 days on a 0 to 3 scale (0=not at all to 3=very much). The total score was calculated for ODD/CD overall (sum of ratings for items 1-17, divided by 17). Higher scores indicate higher severity of symptoms.

  • Investigator-Rated Individual Target Behaviors (ITB-Inv): Intensity Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    ITB-Inv assesses frequency and intensity of individually-defined target behaviors. The investigator defines 3 individual behavior problems based on interviews and additional information. Those most impairing for the child or stressful for the parents will be chosen as target behavior. Intensity during the last 7 days is rated on a 10-point scale (0=no problems to 9=most severe problems) with the lowest possible score of 0 and the highest possible of 27.

  • Investigator-Rated Individual Target Behaviors (ITB-Inv): Frequency Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    ITB-Inv assesses frequency and intensity of individually-defined target behaviors. The investigator defines 3 individual behavior problems based on interviews and additional information. Those most impairing for the child or stressful for the parents will be chosen as target behavior. Frequency of each target behavior during the last 7 days is rated on a 6-point scale (0=never to 5=always) with 0 as lowest possible score and 15 the highest possible score.

  • Impact on Family Scale (FaBel), Total Impact Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    Family burden is assessed by the FaBel questionnaire (German version of the Impact on Family Scale). Questionnaire is answered by participant's caregiver and contains 33 Likert-scaled items to assess general negative impact (of a disability, disorder, disease) on parents, description of social relationships, concern for siblings, financial impact, problems in coping as well as a total score. Each item is rated on a 4-point scale (1=fully applies, 4=applies not at all). Total scores range from 24-96. Higher scores correspond to higher family burden.

  • Clinical Global Impressions - Severity (CGI-S): ADHD Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The physician-rated CGI-S ADHD measures the participant's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients) during the last 7 days.

  • Clinical Global Impressions - Severity (CGI-S): ODD Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The physician-rated CGI-S ODD measures the participant's overall severity of ODD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients) during the last 7 days.

  • Clinical Global Impressions - Severity (CGI-S): Combined ADHD and ODD Scores [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The physician-rated CGI-S Combined ADHD and ODD measures the participant's overall severity of both ADHD and ODD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients) during the last 7 days.

  • German Revised Children's Quality of Life Questionnaire (KINDL-R): Total Quality of Life Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    KINDL-R ("Revidierter KINDer Lebensqualitatsfragebogen, revised version"), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score in the Total QOL score is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher score indicates better QOL.

  • German Revised Children's Quality of Life Questionnaire (KINDL-R): Physical Well-Being Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    KINDL-R ("Revidierter KINDer Lebensqualitatsfragebogen, revised version"), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the Physical Well-Being subscale is 0; highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.

  • German Revised Children's Quality of Life Questionnaire (KINDL-R): Emotional Well-Being Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    KINDL-R ("Revidierter KINDer Lebensqualitatsfragebogen, revised version"), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time).The lowest possible score for the Emotional Well-Being subscale is 0; highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.

  • German Revised Children's Quality of Life Questionnaire (KINDL-R): Self Esteem Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    KINDL-R ("Revidierter KINDer Lebensqualitatsfragebogen, revised version"), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the Self Esteem subscale is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.

  • German Revised Children's Quality of Life Questionnaire (KINDL-R): Family Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    KINDL-R ("Revidierter KINDer Lebensqualitatsfragebogen, revised version"), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1=never; 5=all the time). The lowest possible score on the Family subscale is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.

  • German Revised Children's Quality of Life Questionnaire (KINDL-R): Friends Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    KINDL-R ("Revidierter KINDer Lebensqualitatsfragebogen, revised version"), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the Friends subscale is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.

  • German Revised Children's Quality of Life Questionnaire (KINDL-R): School Score [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    KINDL-R ("Revidierter KINDer Lebensqualitatsfragebogen, revised version"), a validated German quality of life (QOL) questionnaire, provides parents' views on their child's emotional QOL. It consists of 24 items covering 6 QOL related dimensions (subscales) and 7 additional items assessing chronic illness. Each item is rated on a 5-point scale (1= never; 5= all the time). The lowest possible score on the School subscore is 0; the highest possible score is 100. Scores were normalized between 0 and 100, irrespective of the number of items per subscore. Higher scores indicate better QOL.

  • Number of Participants Discontinuing Treatment [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    Originally, time to treatment discontinuation was analyzed, deeming participants 'censored' if they reached the end of the observation period, were lost to followup, or withdrew informed consent. Because the median was not reached, the number of participants who discontinued (i.e., those who were not censored) is reported here.

  • Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    Number of participants who experienced pre-specified categories of clinically relevant adverse events during the initial three-weeks of study treatment. NOTE: this is a subset of the overall adverse events which are reported by participant and event.

  • Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
    Number of participants who experienced pre-specified categories of clinically relevant adverse events during the nine-week study treatment period. NOTE: this is a subset of the overall adverse events which are reported by participant and event.


Enrollment: 181
Study Start Date: November 2006
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atomoxetine Fast Titration
0.5 milligram per kilogram (mg/kg) daily dose taken orally for 1 week, then 1.2 mg/kg daily dose taken orally for 8 weeks
Drug: Atomoxetine
Dosage form for the atomoxetine fast and slow titration arms consists of 2.5 mg, 10 mg, 20 mg, 25 mg, and 40 mg capsules. Double-blind treatment will consist of 3 capsules taken once per day for approximately 9 weeks.
Other Names:
  • LY139603
  • Strattera
Experimental: Atomoxetine Slow Titration
0.5 mg/kg daily dose taken orally for 1 week, then 0.8 mg/kg daily dose taken orally for 1 week, then 1.2 mg/kg daily dose taken orally for 7 weeks
Drug: Atomoxetine
Dosage form for the atomoxetine fast and slow titration arms consists of 2.5 mg, 10 mg, 20 mg, 25 mg, and 40 mg capsules. Double-blind treatment will consist of 3 capsules taken once per day for approximately 9 weeks.
Other Names:
  • LY139603
  • Strattera
Placebo Comparator: Placebo
matching placebo daily dose taken orally
Drug: Placebo
Double-blind treatment will consist of 3 matching placebo capsules taken once per day by mouth for approximately 9 weeks.

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female outpatients who are at least 6 years of age, and who will not have reached their 18th birthday
  • Diagnosis of ADHD and presence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria A through C for ODD (NOTE: diagnosis for conduct disorder not exclusionary)
  • Normal intelligence
  • Able to swallow capsules

Exclusion Criteria:

  • Weigh less than 20 kilogram (kg) or more than 90 kg at study entry
  • Prior treatment with atomoxetine
  • History of seizure disorder, suicidal risk, alcohol or drug abuse within the past 3 months
  • History of severe allergies or multiple adverse drug reactions
  • Cardiovascular disorders: hypertension, unexplained cardiac signs or symptoms, QT (measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle) prolongation , inherited cardiac disorders
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00406354

Locations
Germany
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.
Berlin, Germany, 10789
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.
Dusseldorf, Germany, 40215
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.
Fulda, Germany, 36037
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.
Hamburg, Germany, 22459
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.
Heppenheim, Germany, 64646
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.
Munchen, Germany, 80639
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

Additional Information:
No publications provided

Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00406354     History of Changes
Other Study ID Numbers: 11149, B4Z-SB-LYDW
Study First Received: November 29, 2006
Results First Received: January 14, 2010
Last Updated: February 19, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Attention Deficit and Disruptive Behavior Disorders
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Atomoxetine
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014