An Italian Study of the Efficacy of Atomoxetine in the Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Comorbid Oppositional Defiant Disorder (ODD).

This study has been completed.

Sponsor:

Information provided by:

Eli Lilly and Company

ClinicalTrials.gov Identifier:

NCT00192023

First received: September 12, 2005

Last updated: December 9, 2009

Last verified: December 2009

History of Changes

Results First Received: May 15, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: 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 0.5 mg/kg/day Drug: placebo Drug: atomoxetine 1.2 mg/kg/day Drug: atomoxetine 1.2-1.4 mg/kg/day

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=Screening. Study Period II=Standardized behavioral management program for parents (156 entered, 17 discontinued). Study Period III=Double-Blind (randomization). Two patients did not have post-baseline values for the primary endpoint and were not included in Baseline or efficacy analyses. Study Period IV=Optional open-label phase.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Placebo	placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Participant Flow for 2 periods

Period 1: Period III - Double-Blind

	Atomoxetine	Placebo
STARTED	107	32
COMPLETED	100 ^[1]	32 ^[2]
NOT COMPLETED	7	0
Adverse Event	3	0
Physician Decision	2	0
Parent/Caregiver Decision	2	0

[1]	6 patients who completed the protocol did not enter optional open-label period.
[2]	2 patients who completed the protocol did not enter the optional open-label period.

Period 2: Period IV - Optional Open-Label

	Atomoxetine	Placebo
STARTED	124	0 ^[1]
COMPLETED	49	0
NOT COMPLETED	75	0
Adverse Event	6	0
Lack of Efficacy	7	0
Patient/Caregiver Decision	46	0
Lost to Follow-up	2	0
Protocol Violation	1	0
Withdrawal by Subject	4	0
Physician Decision	9	0

[1]	Placebo patients received atomoxetine during the optional open-label period.

Baseline Characteristics

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Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Placebo	placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Total	Total of all reporting groups

Baseline Measures

	Atomoxetine	Placebo	Total
Number of Participants [units: participants]	105	32	137
Age [units: years] Mean ± Standard Deviation	9.7 ± 2.2	10.0 ± 2.4	9.8 ± 2.3
Gender [units: participants]
Female	7	3	10
Male	98	29	127
Region of Enrollment [units: participants]
Italy	105	32	137
Race/Ethnicity [units: participants]
Caucasian	104	29	133
Hispanic	1	3	4
Height [units: centimeters] Mean ± Standard Deviation	140.1 ± 15.2	141.6 ± 15.3	140.4 ± 15.1
Weight [units: kilograms] Mean ± Standard Deviation	39.3 ± 15.8	41.4 ± 14.1	39.8 ± 15.4

Outcome Measures

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1. Primary:

Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale [ Time Frame: Visit 8 (baseline) and Visit 14 (8 weeks) ]

Measure Type	Primary
Measure Title	Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale
Measure Description	Items from the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for ADHD are included for the two subsets of symptoms: inattention (items #1-#9) and hyperactivity/impulsivity (items #11-#19). The SNAP-IV is based on a 0 (not at all) to 3 (very much) rating scale. Total subscale scores range from 0 to 54.
Time Frame	Visit 8 (baseline) and Visit 14 (8 weeks)
Safety Issue	No

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.
Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e, 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Placebo	placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Measured Values

	Atomoxetine	Placebo
Number of Participants Analyzed [units: participants]	105	32
Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale [units: units on a scale] Mean ± Standard Deviation
Baseline	42.7 ± 6.2	41.5 ± 6.9
Change to 8 Week Endpoint	-8.1 ± 9.2	-2.0 ± 4.7

Statistical Analysis 1 for Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Using an estimate of the common standard deviation of 13 points, the planned sample size will give about 80% power to detect a difference between the groups of 8 points on the SNAP-IV. The sample size was determined using a two-sided test with p=0.05, and assumes that up to 10% of patients will discontinue the study without providing post-baseline efficacy data in Study Period III.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Change to Week 8 Endpoint. Change = Endpoint minus baseline. Model: Change to Week 8=score at Week 8+treatment+site+treatment-by-site interaction. If treatment-by-site interaction isn't significant it will be removed from model.

2. Secondary:

Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity [ Time Frame: Visit 8 (baseline) and Visit 14 (8 weeks) ]

Measure Type	Secondary
Measure Title	Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity
Measure Description	Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients.
Time Frame	Visit 8 (baseline) and Visit 14 (8 weeks)
Safety Issue	No

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.
Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e, 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Placebo	placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Measured Values

	Atomoxetine	Placebo
Number of Participants Analyzed [units: participants]	105	32
Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity [units: units on a scale] Mean ± Standard Deviation
Baseline	5.1 ± 0.8	5.1 ± 0.9
Change to 8 Week Endpoint	-0.6 ± 0.7	0.0 ± 0.5

Statistical Analysis 1 for Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

3. Secondary:

Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale [ Time Frame: Visit 8 (baseline) and Visit 14 (8 weeks) ]

Measure Type	Secondary
Measure Title	Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale
Measure Description	Items are included from the DSM-IV criteria for Oppositional Defiant Disorder (items #21-#28). The SNAP-IV is based on a 0 (not at all) to 3 (very much) rating scale. Total subscale scores range from 0 to 24.
Time Frame	Visit 8 (baseline) and Visit 14 (8 weeks)
Safety Issue	No

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.
Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e, 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Placebo	placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Measured Values

	Atomoxetine	Placebo
Number of Participants Analyzed [units: participants]	105	32
Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale [units: units on a scale] Mean ± Standard Deviation
Baseline	17.2 ± 3.0	17.5 ± 3.8
Change to 8 Week Endpoint	-2.7 ± 4.1	-0.3 ± 2.6

Statistical Analysis 1 for Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

4. Secondary:

Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score [ Time Frame: Visit 8 (baseline) and Visit 14 (8 weeks) ]

Measure Type	Secondary
Measure Title	Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score
Measure Description	The scale measures symptoms of DSM-IV linked anxiety disorders in children. Contains 41 items. Individual item scores range from 0 (not true or hardly ever true) to 2 (very true or often true). Therefore, the overall score ranges from 0 to 82. Higher scores are more indicative of greater anxiety.
Time Frame	Visit 8 (baseline) and Visit 14 (8 weeks)
Safety Issue	No

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.
Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e., 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied. Missing data were not imputed, which generates different analysis population sizes for the different endpoints.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Placebo	placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Measured Values

	Atomoxetine	Placebo
Number of Participants Analyzed [units: participants]	103	32
Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score [units: units on a scale] Mean ± Standard Deviation
Baseline	20.3 ± 11.8	18.8 ± 11.5
Change to 8 Week Endpoint	-2.1 ± 7.6	-1.7 ± 6.5

Statistical Analysis 1 for Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.836

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

5. Secondary:

Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised [ Time Frame: Visit 8 (baseline) and Visit 14 (8 weeks) ]

Measure Type	Secondary
Measure Title	Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised
Measure Description	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.
Time Frame	Visit 8 (baseline) and Visit 14 (8 weeks)
Safety Issue	No

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.
Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e, 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Placebo	placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Measured Values

	Atomoxetine	Placebo
Number of Participants Analyzed [units: participants]	105	32
Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised [units: units on a scale] Mean ± Standard Deviation
Baseline	28.0 ± 8.4	26.9 ± 8.1
Change to 8 Week Endpoint	-0.5 ± 4.4	-0.1 ± 5.0

Statistical Analysis 1 for Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.870

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

6. Secondary:

Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores [ Time Frame: Visit 8 (baseline) and Visit 14 (8 weeks) ]

Measure Type	Secondary
Measure Title	Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores
Measure Description	A 27-item rating scale (0 [not at all/never] to 3 [very much true/very often]) completed by the parent to assess problem behaviors related to ADHD. Subscales: Oppositional, Cognitive Problems, Hyperactivity, and ADHD Index. Subscale total scores range from 0 to 18 for all subscales except ADHD Index which ranges from 0 to 36.
Time Frame	Visit 8 (baseline) and Visit 14 (8 weeks)
Safety Issue	No

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.
Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e., 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied. Missing data were not imputed, which generates different analysis population sizes for the different endpoints.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Placebo	placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Measured Values

	Atomoxetine	Placebo
Number of Participants Analyzed [units: participants]	103	32
Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores [units: units on a scale] Mean ± Standard Deviation
Oppositional Baseline	11.7 ± 3.8	12.2 ± 3.9
Oppositional Change to 8 Week Endpoint	-1.2 ± 3.9	0.8 ± 2.7
Cognitive Problems Baseline	14.3 ± 3.1	14.2 ± 3.2
Cognitive Problems Change to 8 Week Endpoint	-2.3 ± 3.8	0.2 ± 2.6
Hyperactivity Baseline	12.0 ± 3.8	12.0 ± 4.0
Hyperactivity Change to 8 Week Endpoint	-2.2 ± 4.1	-0.7 ± 2.6
ADHD Index Baseline	28.2 ± 4.9	28.4 ± 5.2
ADHD Index Change to 8 Week Endpoint	-5.0 ± 6.7	-0.1 ± 3.9

Statistical Analysis 1 for Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.002

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Oppositional Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

Statistical Analysis 2 for Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Cognitive Problems Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

Statistical Analysis 3 for Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.022

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Hyperactivity Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

Statistical Analysis 4 for Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for ADHD Index Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

7. Secondary:

Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form [ Time Frame: Visit 8 (baseline) and Visit 14 (8 weeks) ]

Measure Type	Secondary
Measure Title	Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form
Measure Description	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. T-score=[(score-4.2382)*10/0.32835] + 50. Higher scores mean improvement.
Time Frame	Visit 8 (baseline) and Visit 14 (8 weeks)
Safety Issue	No

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.
Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e., 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied. Missing data were not imputed, which generates different analysis population sizes for the different endpoints.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Placebo	placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Measured Values

	Atomoxetine	Placebo
Number of Participants Analyzed [units: participants]	97	29
Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form [units: standard deviation units] Mean ± Standard Deviation
Baseline	27.1 ± 10.4	26.9 ± 11.2
Change to 8 Week Endpoint	3.6 ± 8.0	1.2 ± 6.6

Statistical Analysis 1 for Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.071

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

8. Secondary:

Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores [ Time Frame: Visit 8 (baseline) and Visit 14 (8 weeks) ]

Measure Type	Secondary
Measure Title	Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores
Measure Description	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.
Time Frame	Visit 8 (baseline) and Visit 14 (8 weeks)
Safety Issue	No

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.
Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e., 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied. Missing data were not imputed, which generates different analysis population sizes for the different endpoints.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.
Placebo	placebo, daily (QD), by mouth (PO) for 8 weeks, then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Measured Values

	Atomoxetine	Placebo
Number of Participants Analyzed [units: participants]	58	18
Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores [units: units on a scale] Mean ± Standard Deviation
Oppositional Baseline	7.6 ± 4.3	10.8 ± 3.8
Oppositional Change to 8 Week Endpoint	-1.1 ± 2.9	0.1 ± 2.2
Cognitive Problems Baseline	8.2 ± 4.3	8.5 ± 3.7
Cognitive Problems Change to 8 Week Endpoint	-0.9 ± 2.5	0.0 ± 1.7
Hyperactivity Baseline	12.8 ± 5.5	16.3 ± 3.4
Hyperactivity Change to 8 Week Endpoint	-2.1 ± 4.7	-1.1 ± 3.0
ADHD Index Baseline	25.3 ± 8.4	29.4 ± 6.0
ADHD Index Change to 8 Week Endpoint	-3.5 ± 7.1	-0.9 ± 3.3

Statistical Analysis 1 for Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.002

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Oppositional Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

Statistical Analysis 2 for Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.113

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Cognitive Problems Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

Statistical Analysis 3 for Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.051

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Hyperactivity Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

Statistical Analysis 4 for Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.061

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for ADHD Index Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site.

9. Other Pre-specified:

Open-Label Phase Serious Adverse Events [ Time Frame: Baseline (Visit 14) though 1.5 years (Visit 20) or until atomoxetine received marketing approval ]

Measure Type	Other Pre-specified
Measure Title	Open-Label Phase Serious Adverse Events
Measure Description	Number of participants with serious adverse events during the open-label phase of the trial, which was for 1.5 years or until atomoxetine received marketing approval.
Time Frame	Baseline (Visit 14) though 1.5 years (Visit 20) or until atomoxetine received marketing approval
Safety Issue	Yes

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.
Number of patients who entered this optional open-label phase. All of the patients were dispensed drug.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Measured Values

	Atomoxetine
Number of Participants Analyzed [units: participants]	124
Open-Label Phase Serious Adverse Events [units: participants]
Vomiting	1
Infectious mononucleosis	1
Agitation	1

No statistical analysis provided for Open-Label Phase Serious Adverse Events

10. Other Pre-specified:

Open-Label Phase Nonserious Adverse Events [ Time Frame: Baseline (Visit 14) though 1.5 years (Visit 20) or until atomoxetine received marketing approval ]

Measure Type	Other Pre-specified
Measure Title	Open-Label Phase Nonserious Adverse Events
Measure Description	Number of participants with nonserious adverse events during the open-label phase of the trial, which was for 1.5 years or until atomoxetine received marketing approval.
Time Frame	Baseline (Visit 14) though 1.5 years (Visit 20) or until atomoxetine received marketing approval
Safety Issue	Yes

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.
Number of patients who entered this optional open-label phase. All of the patients were dispensed drug.

Reporting Groups

	Description
Atomoxetine	atomoxetine 0.5 mg/kg/day daily (QD), by mouth (PO) for 1 week, 1.2 mg/kg/day QD, PO for 7 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1.5 years or until atomoxetine received marketing approval.

Measured Values

	Atomoxetine
Number of Participants Analyzed [units: participants]	124
Open-Label Phase Nonserious Adverse Events [units: participants]
Abdominal pain	6
Nausea	10
Vomiting	11
Pyrexia	6
Influenza	7
Weight decreased	5
Anorexia	10
Decreased appetite	7
Headache	19
Somnolence	8
Agitation	7
Insomnia	4

No statistical analysis provided for Open-Label Phase Nonserious Adverse Events

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

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
Due to the open-ended timing of the open-label period (up to 1.5 years or until commercial availability) the efficacy data from the open-label extension phase is not included except for adverse event data.

Results Point of Contact:

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

No publications provided

Responsible Party:	Chielf Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT00192023 History of Changes
Other Study ID Numbers:	8856, B4Z-IT-LYCY
Study First Received:	September 12, 2005
Results First Received:	May 15, 2009
Last Updated:	December 9, 2009
Health Authority:	Italy: Ministry of Health

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