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

History of Changes

Results First Received: January 14, 2010

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
Conditions:	Attention Deficit Hyperactivity Disorder Oppositional Defiant Disorder
Interventions:	Drug: Atomoxetine Drug: Placebo

Participant Flow

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Baseline Characteristics

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Reporting Groups

	Description
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
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
Placebo	matching placebo daily dose taken orally
Total	Total of all reporting groups

Baseline Measures

	Atomoxetine Fast Titration	Atomoxetine Slow Titration	Placebo	Total
Number of Participants [units: participants]	60	61	59	180
Age [units: years] Mean ± Standard Deviation	11.1 ± 2.88	10.8 ± 3.39	11.1 ± 2.77	11.0 ± 3.01
Gender [units: participants]
Female	9	8	11	28
Male	51	53	48	152
Race/Ethnicity, Customized [units: participants]
Caucasian	60	60	58	178
African	0	1	1	2
Region of Enrollment [units: participants]
Germany	60	61	59	180
Prior Therapy: Attention-Deficit/Hyperactive Disorder (ADHD), Oppositional Defiant Disorder (ODD) ^[1] [units: participants]
Previous treatment with stimulants	23	28	29	80
Previous psychotropic medication	3	0	3	6
Previous non-drug treatment	6	9	9	24
Previous psychotherapy	8	7	5	20
Summary of ADHD Diagnosis ^[2] [units: participants]
ADHD - combined type	44	45	47	136
ADHD - predominantly inattentive type	13	14	8	35
ADHD - predominantly hyperactive-impulsive type	3	2	4	9
Summary of ODD Diagnosis ^[3] [units: participants]
Conduct disorder	14	16	14	44
Oppositional defiant disorder	44	45	45	134
Disruptive behavior disorder not specified	1	0	0	1
Adjustment disorder, emotion, conduct disturbance	1	0	0	1
Clinical Global Impressions - Severity (CGI-S): ADHD Score ^[4] [units: units on a scale] Mean ± Standard Deviation	5.0 ± 0.77	5.2 ± 0.79	5.1 ± 0.74	5.1 ± 0.77
Clinical Global Impressions - Severity (CGI-S): Combined ADHD and ODD Scores ^[5] [units: units on a scale] Mean ± Standard Deviation	4.9 ± 0.77	5.4 ± 0.73	5.1 ± 0.71	5.1 ± 0.76
Clinical Global Impressions - Severity (CGI-S): ODD Score ^[6] [units: units on a scale] Mean ± Standard Deviation	4.9 ± 0.92	5.3 ± 0.83	5.0 ± 0.86	5.1 ± 0.88
German Revised Children's Quality of Life Questionnaire (KINDL-R): Emotional Well-Being Score ^[7] [units: units on a scale] Mean ± Standard Deviation	72.9 ± 18.58	72.5 ± 17.28	70.1 ± 15.92	71.9 ± 17.22
German Revised Children's Quality of Life Questionnaire (KINDL-R): Family Score ^[8] [units: units on a scale] Mean ± Standard Deviation	58.7 ± 20.17	57.6 ± 20.73	52.3 ± 20.50	56.2 ± 20.55
German Revised Children's Quality of Life Questionnaire (KINDL-R): Friends Score ^[9] [units: units on a scale] Mean ± Standard Deviation	58.2 ± 21.56	53.9 ± 21.23	54.2 ± 23.34	55.4 ± 22.02
German Revised Children's Quality of Life Questionnaire (KINDL-R): Physical Well-Being Score ^[10] [units: units on a scale] Mean ± Standard Deviation	79.8 ± 18.53	75.9 ± 19.99	81.5 ± 16.78	79.0 ± 18.54
German Revised Children's Quality of Life Questionnaire (KINDL-R): School Score ^[11] [units: units on a scale] Mean ± Standard Deviation	62.2 ± 16.74	61.5 ± 20.62	62.4 ± 15.06	62.0 ± 17.50
German Revised Children's Quality of Life Questionnaire (KINDL-R): Self Esteem Score ^[12] [units: units on a scale] Mean ± Standard Deviation	55.4 ± 18.48	52.0 ± 18.71	50.4 ± 18.92	52.6 ± 18.71
German Revised Children's Quality of Life Questionnaire (KINDL-R): Total Quality of Life Score ^[13] [units: units on a scale] Mean ± Standard Deviation	64.5 ± 12.43	62.4 ± 12.92	61.8 ± 13.02	62.9 ± 12.78
Impact on Family Scale (FaBel): Total Impact Score ^[14] [units: units on a scale] Mean ± Standard Deviation	53.3 ± 12.88	54.1 ± 13.15	53.9 ± 12.83	53.8 ± 12.89
Investigator-Rated Individual Target Behaviors (ITB-Inv): Frequency Score ^[15] [units: units on a scale] Mean ± Standard Deviation	10.9 ± 2.03	11.4 ± 2.06	11.3 ± 2.67	11.2 ± 2.27
Investigator-Rated Individual Target Behaviors (ITB-Inv): Intensity Score ^[16] [units: units on a scale] Mean ± Standard Deviation	21.3 ± 3.62	22.1 ± 3.39	20.5 ± 3.57	21.3 ± 3.56
Parent-Rated Attention-Deficit Scale (FBB-HKS): Total Score, Severity ^[17] [units: units on a scale] Mean ± Standard Deviation	2.0 ± 0.62	2.0 ± 0.54	1.9 ± 0.52	2.0 ± 0.56
Parent-Rated Oppositional Defiant/Conduct Disorders Scale (FBB-SSV): Total Score, Severity ^[18] [units: units on a scale] Mean ± Standard Deviation	1.4 ± 0.53	1.4 ± 0.49	1.4 ± 0.56	1.4 ± 0.52
Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Inattention Subscale Score ^[19] [units: units on a scale] Mean ± Standard Deviation	17.7 ± 5.23	18.3 ± 4.91	17.5 ± 4.94	17.9 ± 5.01
Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): Hyperactivity/Impulsivity Score ^[20] [units: units on a scale] Mean ± Standard Deviation	19.9 ± 4.98	19.7 ± 4.76	18.9 ± 4.85	19.5 ± 4.85
Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ODD Score ^[21] [units: units on a scale] Mean ± Standard Deviation	15.5 ± 4.07	15.6 ± 3.82	15.6 ± 5.13	15.5 ± 4.35
Swanson, Nolan & Pelham Rating Scale-Revised (SNAP-IV): ADHD Combined Score ^[22] [units: units on a scale] Mean ± Standard Deviation	37.6 ± 9.70	38.0 ± 8.91	36.4 ± 9.31	37.3 ± 9.28

[1]	Summarizes number of participants who received previous attention-deficit/hyperactive disorder (ADHD) and/or oppositional defiant disorder (ODD) therapy, by medication and non-medication categories. NOTE: Because some participants may have received one or more types of ADHD and/or ODD therapies while others may not, the breakdown of prior therapies by treatment group does not equal the number of participants in each treatment group.
[2]	Breakdown of ADHD diagnosis in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).
[3]	Breakdown of ODD diagnosis in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).
[4]	The physician-rated CGI-S ADHD subscale 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.
[5]	The physician-rated CGI-S Combined ADHD and ODD subscale 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.
[6]	The physician-rated CGI-S ODD subscale 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.
[7]	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). Lowest possible score for the Emotional Well-Being 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.
[8]	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.
[9]	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.
[10]	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.
[11]	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 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.
[12]	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.
[13]	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 scores indicate better QOL.
[14]	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.
[15]	ITB-Inv assesses frequency and intensity of individually-defined target behaviors. The investigator defines 3 individual behavior problems based on interviews & 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.
[16]	ITB-Inv assesses frequency and intensity of individually-defined target behaviors. The investigator defines 3 individual behavior problems based on interviews & 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.
[17]	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). High scores indicate high severity of symptoms.
[18]	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.
[19]	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.
[20]	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.
[21]	The SNAP-IV, ODD subscale (items 19-26) 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 24.
[22]	SNAP-IV is a 26-item scale that includes 1 item for each of 18 symptoms in the DSM-IV diagnosis of ADHD and 1 item for each of 8 symptoms 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). SNAP-IV yields scores in 3 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). SNAP-IV ADHD combined score (inattention + hyperactivity/impulsivity) range=0-54.

Outcome Measures

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1. Primary:

Swanson, Nolan and Pelham Rating Scale Revised (SNAP-IV) Oppositional Defiant Disorder: (ODD) Score [ Time Frame: 9 weeks ]

Show Outcome Measure 1

2. Secondary:

Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Combined Score [ Time Frame: 9 weeks ]

Show Outcome Measure 2

3. Secondary:

Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Inattention Score [ Time Frame: 9 weeks ]

Show Outcome Measure 3

4. Secondary:

Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): Hyperactivity/Impulsivity Score [ Time Frame: 9 weeks ]

Show Outcome Measure 4

5. Secondary:

Parent-Rated Attention-Deficit Scale (FBB-HKS), Total Score: Severity [ Time Frame: 9 weeks ]

Show Outcome Measure 5

6. Secondary:

Parent-Rated Oppositional Defiant/Conduct Disorders Scale (FBB-SSV): Total Score, Severity [ Time Frame: 9 weeks ]

Show Outcome Measure 6

7. Secondary:

Investigator-Rated Individual Target Behaviors (ITB-Inv): Intensity Score [ Time Frame: 9 weeks ]

Show Outcome Measure 7

8. Secondary:

Investigator-Rated Individual Target Behaviors (ITB-Inv): Frequency Score [ Time Frame: 9 weeks ]

Show Outcome Measure 8

9. Secondary:

Impact on Family Scale (FaBel), Total Impact Score [ Time Frame: 9 weeks ]

Show Outcome Measure 9

10. Secondary:

Clinical Global Impressions - Severity (CGI-S): ADHD Score [ Time Frame: 9 weeks ]

Show Outcome Measure 10

11. Secondary:

Clinical Global Impressions - Severity (CGI-S): ODD Score [ Time Frame: 9 weeks ]

Show Outcome Measure 11

12. Secondary:

Clinical Global Impressions - Severity (CGI-S): Combined ADHD and ODD Scores [ Time Frame: 9 weeks ]

Show Outcome Measure 12

13. Secondary:

German Revised Children's Quality of Life Questionnaire (KINDL-R): Total Quality of Life Score [ Time Frame: 9 weeks ]

Show Outcome Measure 13

14. Secondary:

German Revised Children's Quality of Life Questionnaire (KINDL-R): Physical Well-Being Score [ Time Frame: 9 weeks ]

Show Outcome Measure 14

15. Secondary:

German Revised Children's Quality of Life Questionnaire (KINDL-R): Emotional Well-Being Score [ Time Frame: 9 weeks ]

Show Outcome Measure 15

16. Secondary:

German Revised Children's Quality of Life Questionnaire (KINDL-R): Self Esteem Score [ Time Frame: 9 weeks ]

Show Outcome Measure 16

17. Secondary:

German Revised Children's Quality of Life Questionnaire (KINDL-R): Family Score [ Time Frame: 9 weeks ]

Show Outcome Measure 17

18. Secondary:

German Revised Children's Quality of Life Questionnaire (KINDL-R): Friends Score [ Time Frame: 9 weeks ]

Show Outcome Measure 18

19. Secondary:

German Revised Children's Quality of Life Questionnaire (KINDL-R): School Score [ Time Frame: 9 weeks ]

Show Outcome Measure 19

20. Secondary:

Number of Participants Discontinuing Treatment [ Time Frame: 9 weeks ]

Show Outcome Measure 20

21. Secondary:

Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Initial Three Weeks of Study Treatment [ Time Frame: 3 weeks ]

Show Outcome Measure 21

22. Secondary:

Number of Patients Who Experienced Clinically Relevant Categories of Adverse Events During Nine-Week Study Treatment Period [ Time Frame: 9 weeks ]

Show Outcome Measure 22

Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

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
No text entered.

Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 1-800-545-5979

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

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