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

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00320528
First received: April 28, 2006
Last updated: December 2, 2009
Last verified: December 2009
Results First Received: September 30, 2009  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Attention Deficit Disorder With Hyperactivity
Intervention: Drug: atomoxetine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Study Period I was a 3-day screening period. Study Period II was 12 weeks long. Study Period III was an optional additional 12 week open-label extension. Results are presented for Period II (patients who received at least one dose of study drug).

Reporting Groups
  Description
Pure ADHD 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
ADHD+Internalizing Disorders 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
ADHD+Externalizing Disorders 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

Participant Flow for 2 periods

Period 1:   Study Period II
    Pure ADHD   ADHD+Internalizing Disorders   ADHD+Externalizing Disorders
STARTED   98   41   130 
Received at Least One Dose of Study Drug   97   38   128 
COMPLETED   87   31   108 
NOT COMPLETED   11   10   22 
Adverse Event                3                4                8 
Parent/Caregiver Decision                8                3                11 
Withdrawal by Subject                0                1                1 
Entry Criteria Exclusion                0                2                2 

Period 2:   Study Period III
    Pure ADHD   ADHD+Internalizing Disorders   ADHD+Externalizing Disorders
STARTED   87   31   108 
COMPLETED   0   0   2 
NOT COMPLETED   87   31   106 
Adverse Event                1                0                0 
Lost to Follow-up                1                0                0 
Withdrawal by Subject                1                1                2 
Lack of Efficacy                2                0                0 
Parent/Caregiver Decision                14                3                11 
Protocol Violation                0                1                0 
Physician Decision                0                1                2 
Sponsor Decision                0                0                1 
Atomoxetine Commercially Available                68                25                90 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pure ADHD 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
ADHD+Internalizing Disorders 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
ADHD+Externalizing Disorders 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
Total Total of all reporting groups

Baseline Measures
   Pure ADHD   ADHD+Internalizing Disorders   ADHD+Externalizing Disorders   Total 
Overall Participants Analyzed 
[Units: Participants]
 97   38   128   263 
Age 
[Units: Years]
Mean (Standard Deviation)
 10.12  (2.51)   10.42  (2.41)   10.00  (2.57)   10.11  (2.51) 
Gender 
[Units: Participants]
       
Female   14   3   9   26 
Male   83   35   119   237 
Region of Enrollment 
[Units: Participants]
       
Italy   97   38   128   263 
Race/Ethnicity 
[Units: Participants]
       
Caucasian   90   36   124   250 
Hispanic   1   2   2   5 
African   3   0   0   3 
Native American   1   0   2   3 
East Asian   2   0   0   2 
Child Health and Illness Profile - Child Edition (CHIP-CE) - Achievement Domain [1] 
[Units: T-Score]
Mean (Standard Deviation)
       
Achievement Domain (N=96, N=33, N=121)   29.27  (7.89)   27.72  (7.73)   25.83  (7.60)   27.40  (7.86) 
Satisfaction Domain (N=96, N=24, N=122)   39.26  (13.89)   30.11  (14.83)   31.69  (14.78)   34.34  (14.91) 
Comfort Domain (N=96, N=35, N=122)   51.31  (9.40)   46.76  (12.28)   44.74  (9.38)   47.51  (10.26) 
Resilience Domain (N=96, N=34, N=123)   39.34  (10.15)   34.96  (10.89)   31.40  (11.85)   34.89  (11.65) 
Risk Avoidance (N=96, N=33, N=121)   32.03  (9.7)   30.48  (12.29)   22.85  (12.00)   27.38  (12.01) 
[1] 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.
Children's Depression Rating Scale-Revised (CDRS-R) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 37.93  (12.26)   43.76  (13.48)   43.06  (13.69)   41.26  (13.35) 
[1] 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.
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 4.64  (0.79)   4.97  (0.79)   4.98  (0.78)   4.85  (0.80) 
[1] Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).
Conners' Teacher Rating Scale-Revised:Short Form (CTRS-R:S) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
       
Oppositional   5.97  (4.93)   4.97  (4.66)   8.62  (4.83)   7.10  (5.05) 
Cognitive Problems   7.86  (3.73)   7.68  (3.80)   7.96  (3.61)   7.88  (3.67) 
Hyperactivity   11.38  (6.09)   12.03  (5.21)   14.67  (5.15)   13.05  (5.74) 
ADHD Index   22.14  (6.86)   22.94  (6.01)   25.18  (6.07)   23.70  (6.52) 
[1] 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.
Pediatric Anxiety Rating Scale (PARS) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 2.50  (2.67)   7.50  (5.68)   4.67  (5.12)   4.28  (4.76) 
[1] 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.
Swanson, Nolan, and Pelham Rating Scale Revised (SNAP-IV) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
       
Inattention Subscale (N=97, N=38, N=127)   20.28  (4.19)   21.03  (3.72)   21.87  (3.48)   21.16  (3.85) 
Hyperactivity/Impulsivity Subscale (N=97, N=38, N=   17.21  (6.10)   19.66  (5.54)   21.04  (3.48)   19.42  (5.19) 
Combined Type Subscale (N=97, N=38, N=127)   37.48  (7.78)   40.68  (7.87)   42.91  (5.51)   40.58  (7.20) 
Oppositional Subscale (N=97, N=38, N=127)   10.15  (4.54)   12.32  (4.67)   17.99  (3.57)   14.27  (5.51) 
[1] The SNAP-IV is a 26-item scale that 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 score on 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), Hyperactivity/impulsivity (items 10-18: subscale range=0-27), and Oppositional (items 19-26: subscale range=0-24). Combined type (inattention + hyperactivity/impulsivity) scores range from 0-54.


  Outcome Measures
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1.  Primary:   Change From Baseline to 12 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE), Achievement Domain   [ Time Frame: Baseline, 12 Weeks ]

2.  Secondary:   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)   [ Time Frame: Baseline, 12 Weeks ]

3.  Secondary:   Change From Baseline to 12 Week Endpoint in Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S)   [ Time Frame: Baseline, 12 Weeks ]

4.  Secondary:   Change From Baseline to 12 Week Endpoint in CHIP-CE Satisfaction, Comfort, Resilience and Risk Avoidance Domains   [ Time Frame: Baseline, 12 Weeks ]

5.  Secondary:   Change From Baseline to 12 Week Endpoint in Pediatric Anxiety Rating Scale (PARS)   [ Time Frame: Baseline, 12 Weeks ]

6.  Secondary:   Change From Baseline to 12 Week Endpoint in Children's Depression Rating Scale-Revised (CDRS-R)   [ Time Frame: Baseline, 12 Weeks ]

7.  Secondary:   Change From Baseline to 12 Week Endpoint in SNAP-IV Oppositional Scale   [ Time Frame: Baseline, 12 Weeks ]

8.  Secondary:   Change From Baseline to 12 Week Endpoint in Adolescent Symptom Inventory-4: Parent Checklist (ASI-4)   [ Time Frame: Baseline, 12 Weeks ]

9.  Secondary:   Change From Baseline to 12 Week Endpoint in Child Symptom Inventory-4: Parent Checklist (CSI-4)   [ Time Frame: Baseline, 12 Weeks ]

10.  Secondary:   Change From Baseline to 12 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form (CTRS-R:S)   [ Time Frame: Baseline, 12 Weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The original intent was to also calculate change and 95% confidence intervals at end of Period III; however, due to low number of patients completing Period III, variations from baseline (LOCF), are not suitable for further analysis or description.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979



Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00320528     History of Changes
Other Study ID Numbers: 9867
B4Z-IT-LYDS
Study First Received: April 28, 2006
Results First Received: September 30, 2009
Last Updated: December 2, 2009
Health Authority: Italy: Ministry of Health