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).
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00192023
Collaborator
(none)
139
12
2
43
11.6
0.3
Study Details
Study Description
Brief Summary
The study is a phase IIIb multicentre, randomised, placebo controlled, trial in paediatric patients with Attention-Deficit/Hyperactivity (ADHD) and Oppositional Defiant Disorder (ODD). The primary aim of the study is to evaluate the efficacy of atomoxetine in improving ADHD and ODD symptoms in patients non responders to a previous psychological intervention with parent support. Moreover, the potential role of atomoxetine in treating other psychiatric comorbid conditions associated with ADHD and ODD will be assessed.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
139 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
An Italian Randomised, Double-blind Placebo Controlled Study of the Efficacy of Atomoxetine Hydrochloride in the Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder and Comorbid Oppositional Defiant Disorder
Study Start Date
:
Oct 1, 2004
Actual Primary Completion Date
:
Aug 1, 2006
Actual Study Completion Date
:
May 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Atomoxetine atomoxetine 0.5 milligrams per kilogram per day (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 receives marketing approval. |
Drug: atomoxetine 0.5 mg/kg/day
atomoxetine 0.5 milligrams per kilogram per day (mg/kg/day) daily (QD), by mouth (PO)
Other Names:
Drug: atomoxetine 1.2 mg/kg/day
atomoxetine 1.2 mg/kg/day QD, PO
Other Names:
Drug: atomoxetine 1.2-1.4 mg/kg/day
atomoxetine 1.2 - 1.4 mg/kg/day QD, PO
Other Names:
|
| Placebo Comparator: 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 receives marketing approval. |
Drug: atomoxetine 0.5 mg/kg/day
atomoxetine 0.5 milligrams per kilogram per day (mg/kg/day) daily (QD), by mouth (PO)
Other Names:
Drug: placebo
Drug: atomoxetine 1.2-1.4 mg/kg/day
atomoxetine 1.2 - 1.4 mg/kg/day QD, PO
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale [Visit 8 (baseline) and Visit 14 (8 weeks)]
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.
Secondary Outcome Measures
- Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity [Visit 8 (baseline) and Visit 14 (8 weeks)]
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.
- Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale [Visit 8 (baseline) and Visit 14 (8 weeks)]
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.
- Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score [Visit 8 (baseline) and Visit 14 (8 weeks)]
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.
- Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised [Visit 8 (baseline) and Visit 14 (8 weeks)]
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.
- Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores [Visit 8 (baseline) and Visit 14 (8 weeks)]
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.
- Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form [Visit 8 (baseline) and Visit 14 (8 weeks)]
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.
- Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores [Visit 8 (baseline) and Visit 14 (8 weeks)]
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.
Other Outcome Measures
- Open-Label Phase Serious Adverse Events [Baseline (Visit 14) though 1.5 years (Visit 20) or until atomoxetine received marketing approval]
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.
- Open-Label Phase Nonserious Adverse Events [Baseline (Visit 14) though 1.5 years (Visit 20) or until atomoxetine received marketing approval]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
6 Years
to 15 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Child or adolescent patients, male or female outpatients, who are at least 6 years of age, but must not yet have reached their 16th birthday prior to Visit 1, when informed consent is obtained.
-
Patients must meet Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnostic criteria for ADHD (any subtype) and ODD and score at least 1.5 standard deviations above the age norm for their diagnostic subtype using published norms for the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder (SNAP-IV ADHD) Subscale score at both Visit 1 and 2.
-
They must also have a SNAP-IV ODD subscale score of at least 15 at both Visit 1 and Visit 2.
-
Other comorbid conditions, are allowed but the diagnosis of ADHD and ODD must be the patient's primary diagnosis.
-
Patients must be of normal intelligence in the judgment of the investigator (that is, without a general impairment of intelligence and likely, in the investigator's judgement, to achieve a score of greater than or equal to 70 on an Intelligence Quotient (IQ) test). The administration of a formal IQ test is not an entry requirement for the study. Specific learning disabilities are not considered general impairment of intelligence.
Exclusion Criteria:
-
Patients who weigh less than 20 kilograms (kg) at study entry (Visit 1).
-
Patients who have a documented history of Bipolar I or II disorder, any history of psychosis or pervasive development disorder.
-
Patients with a history of any seizure disorder (other than febrile seizures) or patients who have taken (or are currently taking) anticonvulsants for seizure control are not eligible to participate.
-
Patients at serious suicidal risk as assessed by the investigator.
-
Patients who, in the investigator's judgment, are likely to need psychotropic medications apart from the drug under the study, including health-food supplements that the investigator feels have central nervous system activity (for example, St. John's Wort, melatonin).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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. | Alessandria | Italy | ||
| 2 | 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. | Bari | Italy | ||
| 3 | For additional Information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri 9 AM to 5 PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician | Cagliari | Italy | ||
| 4 | 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. | Genova | Italy | ||
| 5 | 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. | Messina | Italy | ||
| 6 | 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. | Napoli | Italy | ||
| 7 | 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. | Padova | Italy | ||
| 8 | 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. | Pavia | Italy | ||
| 9 | 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. | Pisa | Italy | ||
| 10 | 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. | Roma | Italy | ||
| 11 | 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. | S. Vito Tagliamento | Italy | ||
| 12 | 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. | Venezia | Italy |
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
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00192023
Other Study ID Numbers:
- 8856
- B4Z-IT-LYCY
First Posted:
Sep 19, 2005
Last Update Posted:
Jan 18, 2010
Last Verified:
Dec 1, 2009
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Atomoxetine | Placebo |
|---|---|---|
| Arm/Group Description | 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, 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. |
| Period Title: Period III - Double-Blind | ||
| STARTED | 107 | 32 |
| COMPLETED | 100 | 32 |
| NOT COMPLETED | 7 | 0 |
| Period Title: Period III - Double-Blind | ||
| STARTED | 124 | 0 |
| COMPLETED | 49 | 0 |
| NOT COMPLETED | 75 | 0 |
Baseline Characteristics
| Arm/Group Title | Atomoxetine | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | 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, 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 of all reporting groups |
| Overall Participants | 105 | 32 | 137 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
9.7
(2.2)
|
10.0
(2.4)
|
9.8
(2.3)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
7
6.7%
|
3
9.4%
|
10
7.3%
|
| Male |
98
93.3%
|
29
90.6%
|
127
92.7%
|
| Region of Enrollment (participants) [Number] | |||
| Italy |
105
100%
|
32
100%
|
137
100%
|
| Race/Ethnicity (participants) [Number] | |||
| Caucasian |
104
99%
|
29
90.6%
|
133
97.1%
|
| Hispanic |
1
1%
|
3
9.4%
|
4
2.9%
|
| Height (centimeters) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [centimeters] |
140.1
(15.2)
|
141.6
(15.3)
|
140.4
(15.1)
|
| Weight (kilograms) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kilograms] |
39.3
(15.8)
|
41.4
(14.1)
|
39.8
(15.4)
|
Outcome Measures
| Title | Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Atomoxetine | Placebo |
|---|---|---|
| Arm/Group Description | 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, 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. |
| Measure Participants | 105 | 32 |
| 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
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 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. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline to 8 Week Endpoint in Clinical Global Impressions - Attention-Deficit/Hyperactivity Disorder (ADHD) - Severity |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Atomoxetine | Placebo |
|---|---|---|
| Arm/Group Description | 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, 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. |
| Measure Participants | 105 | 32 |
| 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
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-value for Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline to 8 Week Endpoint in SNAP-IV Oppositional Subscale |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Atomoxetine | Placebo |
|---|---|---|
| Arm/Group Description | 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, 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. |
| Measure Participants | 105 | 32 |
| 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
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | P-value for Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline to 8 Week Endpoint in Screen for Child Anxiety Related Emotional Disorders (SCARED) Total Score |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Atomoxetine | Placebo |
|---|---|---|
| Arm/Group Description | 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, 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. |
| Measure Participants | 103 | 32 |
| 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
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.836 |
| Comments | P-value for Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline to 8 Week Endpoint in Children's Depression Rating Scale-Revised |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Atomoxetine | Placebo |
|---|---|---|
| Arm/Group Description | 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, 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. |
| Measure Participants | 105 | 32 |
| 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
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.870 |
| Comments | P-value for Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline to 8 Week Endpoint in Conners' Parent Rating Scale-Revised: Short Form Subscale Scores |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Atomoxetine | Placebo |
|---|---|---|
| Arm/Group Description | 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, 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. |
| Measure Participants | 103 | 32 |
| 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
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | 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. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 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. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.022 |
| Comments | 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. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 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. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline to 8 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE): Parent Rated Form |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Atomoxetine | Placebo |
|---|---|---|
| Arm/Group Description | 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, 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. |
| Measure Participants | 97 | 29 |
| 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
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.071 |
| Comments | P-value for Change to 8 Week Endpoint. Change = Endpoint minus baseline. Model: Change to 8 Week Endpoint=Score at 8 weeks+treatment+site. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline to 8 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form Subscale Scores |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Atomoxetine | Placebo |
|---|---|---|
| Arm/Group Description | 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, 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. |
| Measure Participants | 58 | 18 |
| 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
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | 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. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.113 |
| Comments | 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. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.051 |
| Comments | 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. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Atomoxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.061 |
| Comments | 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. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Open-Label Phase Serious Adverse Events |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of patients who entered this optional open-label phase. All of the patients were dispensed drug. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 124 |
| Vomiting |
1
1%
|
| Infectious mononucleosis |
1
1%
|
| Agitation |
1
1%
|
| Title | Open-Label Phase Nonserious Adverse Events |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of patients who entered this optional open-label phase. All of the patients were dispensed drug. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 124 |
| Abdominal pain |
6
5.7%
|
| Nausea |
10
9.5%
|
| Vomiting |
11
10.5%
|
| Pyrexia |
6
5.7%
|
| Influenza |
7
6.7%
|
| Weight decreased |
5
4.8%
|
| Anorexia |
10
9.5%
|
| Decreased appetite |
7
6.7%
|
| Headache |
19
18.1%
|
| Somnolence |
8
7.6%
|
| Agitation |
7
6.7%
|
| Insomnia |
4
3.8%
|
Adverse Events
| Time Frame | The results in this module are serious (there weren't any) and non-serious adverse events during Study Period III. Adverse events during the Open-Label (Period IV) phase are presented as Other Pre-Specified Outcome Measures. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Atomoxetine | Placebo | ||
| Arm/Group Description | 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, 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. | ||
All Cause Mortality |
||||
| Atomoxetine | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Atomoxetine | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/107 (0%) | 0/32 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Atomoxetine | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 79/107 (73.8%) | 12/32 (37.5%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 11/107 (10.3%) | 13 | 1/32 (3.1%) | 1 |
| Abdominal pain upper | 9/107 (8.4%) | 11 | 4/32 (12.5%) | 4 |
| Diarrhoea | 4/107 (3.7%) | 6 | 2/32 (6.3%) | 2 |
| Nausea | 14/107 (13.1%) | 15 | 0/32 (0%) | 0 |
| Vomiting | 14/107 (13.1%) | 22 | 1/32 (3.1%) | 1 |
| Infections and infestations | ||||
| Influenza | 9/107 (8.4%) | 9 | 0/32 (0%) | 0 |
| Investigations | ||||
| Weight decreased | 6/107 (5.6%) | 6 | 0/32 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 26/107 (24.3%) | 27 | 1/32 (3.1%) | 1 |
| Decreased appetite | 9/107 (8.4%) | 10 | 0/32 (0%) | 0 |
| Nervous system disorders | ||||
| Headache | 18/107 (16.8%) | 22 | 4/32 (12.5%) | 5 |
| Somnolence | 18/107 (16.8%) | 19 | 2/32 (6.3%) | 2 |
| Psychiatric disorders | ||||
| Nervousness | 6/107 (5.6%) | 6 | 1/32 (3.1%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 0/107 (0%) | 0 | 2/32 (6.3%) | 2 |
Limitations/Caveats
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.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00192023
Other Study ID Numbers:
- 8856
- B4Z-IT-LYCY
First Posted:
Sep 19, 2005
Last Update Posted:
Jan 18, 2010
Last Verified:
Dec 1, 2009