Trial Outcomes & Findings for Long-Term Study of Atomoxetine in Children With Attention-Deficit/Hyperactivity Disorder (AD/HD) (NCT NCT00191386)
NCT ID: NCT00191386
Last Updated: 2010-12-28
Results Overview
Details on the actual adverse events are presented in the Reported Adverse Events Section.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
228 participants
Primary outcome timeframe
Baseline through 4 years
Results posted on
2010-12-28
Participant Flow
This ongoing study is being conducted as a follow-up investigation of ADHD pediatric patients who completed Study LYBC (NCT00191295).
Participant milestones
| Measure |
Atomoxetine
0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
|
|---|---|
|
Overall Study
STARTED
|
228
|
|
Overall Study
6 Months
|
183
|
|
Overall Study
12 Months
|
149
|
|
Overall Study
2 Years
|
105
|
|
Overall Study
3 Years
|
65
|
|
Overall Study
COMPLETED
|
68
|
|
Overall Study
NOT COMPLETED
|
160
|
Reasons for withdrawal
| Measure |
Atomoxetine
0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
|
|---|---|
|
Overall Study
Adverse Event
|
16
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Entry Criteria Exclusion
|
3
|
|
Overall Study
Protocol Violation
|
18
|
|
Overall Study
Withdrawal by Subject
|
96
|
|
Overall Study
Physician Decision
|
11
|
|
Overall Study
Lack of Efficacy
|
15
|
Baseline Characteristics
Long-Term Study of Atomoxetine in Children With Attention-Deficit/Hyperactivity Disorder (AD/HD)
Baseline characteristics by cohort
| Measure |
Atomoxetine
n=228 Participants
0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
|
|---|---|
|
Age Continuous
|
10.69 years
STANDARD_DEVIATION 2.48 • n=5 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
195 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
228 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
228 participants
n=5 Participants
|
|
ADHD Rating Scale-IV-Translated in Japanese Parent Version: Investigator Administered/Scored
|
22.23 Units on a scale
STANDARD_DEVIATION 10.42 • n=5 Participants
|
|
Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S)
|
4.00 Units on a scale
STANDARD_DEVIATION 1.04 • n=5 Participants
|
|
Mean Age at Onset of Attention Deficit Hyperactivity Disorder (ADHD)
|
3.93 Years
STANDARD_DEVIATION 1.57 • n=5 Participants
|
|
Age at Onset of ADHD
0 Years
|
1 Participants
n=5 Participants
|
|
Age at Onset of ADHD
1 Years
|
17 Participants
n=5 Participants
|
|
Age at Onset of ADHD
2 Years
|
25 Participants
n=5 Participants
|
|
Age at Onset of ADHD
3 Years
|
49 Participants
n=5 Participants
|
|
Age at Onset of ADHD
4 Years
|
45 Participants
n=5 Participants
|
|
Age at Onset of ADHD
5 Years
|
47 Participants
n=5 Participants
|
|
Age at Onset of ADHD
6 Years
|
40 Participants
n=5 Participants
|
|
Age at Onset of ADHD
7 Years
|
4 Participants
n=5 Participants
|
|
Duration of ADHD
|
6.25 Years
STANDARD_DEVIATION 2.85 • n=5 Participants
|
|
Duration of ADHD
1 Years
|
6 Participants
n=5 Participants
|
|
Duration of ADHD
2 Years
|
8 Participants
n=5 Participants
|
|
Duration of ADHD
3 Years
|
30 Participants
n=5 Participants
|
|
Duration of ADHD
4 Years
|
24 Participants
n=5 Participants
|
|
Duration of ADHD
5 Years
|
32 Participants
n=5 Participants
|
|
Duration of ADHD
6 Years
|
26 Participants
n=5 Participants
|
|
Duration of ADHD
7 Years
|
31 Participants
n=5 Participants
|
|
Duration of ADHD
8 Years
|
21 Participants
n=5 Participants
|
|
Duration of ADHD
9 Years
|
22 Participants
n=5 Participants
|
|
Duration of ADHD
10 Years
|
11 Participants
n=5 Participants
|
|
Duration of ADHD
11 Years
|
4 Participants
n=5 Participants
|
|
Duration of ADHD
12 Years
|
7 Participants
n=5 Participants
|
|
Duration of ADHD
13 Years
|
3 Participants
n=5 Participants
|
|
Duration of ADHD
14 Years
|
3 Participants
n=5 Participants
|
|
Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL
Oppositional Defiant Disorder
|
32 Participants with Disorder Presently
n=5 Participants
|
|
Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL
Conduct Disorder
|
2 Participants with Disorder Presently
n=5 Participants
|
|
Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL
Specific Phobia
|
3 Participants with Disorder Presently
n=5 Participants
|
|
Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL
Generalized Anxiety Disorder
|
1 Participants with Disorder Presently
n=5 Participants
|
|
Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL
Obsessive Compulsive Disorder
|
1 Participants with Disorder Presently
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline through 4 yearsPopulation: All patients who took at least one dose of study medication were included in the analyses of safety data.
Details on the actual adverse events are presented in the Reported Adverse Events Section.
Outcome measures
| Measure |
Atomoxetine
n=228 Participants
0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
|
|---|---|
|
Number of Participants With Adverse Events for Long Term Safety and Tolerability
All Other Nonserious Adverse Events
|
222 Participants
|
|
Number of Participants With Adverse Events for Long Term Safety and Tolerability
Serious Adverse Events
|
6 Participants
|
SECONDARY outcome
Timeframe: Baseline, 6 Months, 12 Months, 2 Years, 3 Years, 4 YearsPopulation: Full Analysis Set: Participants who met Study LYBC criteria, took 1 dose of drug, had a baseline/post-baseline measurement. Changes from baseline used LOCF approach. Baseline was the last non-missing measurement before taking atomoxetine (either LYDA Week 0 or LYBC Week 2). Endpoint was the last non-missing measurement in each assessment period.
Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54.
Outcome measures
| Measure |
Atomoxetine
n=228 Participants
0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
|
|---|---|
|
Change From Baseline at Various Timepoints in Attention Deficit Hyperactivity Disorder Rating Scale-IV-Translated in Japanese Parent Version: Investigator Administered and Scored (ADHDRS-IV-J:I) Total Score
Total Score 6 Months (n=228)
|
-14.1 Units on a scale
Standard Deviation 9.3
|
|
Change From Baseline at Various Timepoints in Attention Deficit Hyperactivity Disorder Rating Scale-IV-Translated in Japanese Parent Version: Investigator Administered and Scored (ADHDRS-IV-J:I) Total Score
Total Score 12 Months (n=178)
|
-16.0 Units on a scale
Standard Deviation 9.2
|
|
Change From Baseline at Various Timepoints in Attention Deficit Hyperactivity Disorder Rating Scale-IV-Translated in Japanese Parent Version: Investigator Administered and Scored (ADHDRS-IV-J:I) Total Score
Total Score 2 Years (n=143)
|
-17.7 Units on a scale
Standard Deviation 9.4
|
|
Change From Baseline at Various Timepoints in Attention Deficit Hyperactivity Disorder Rating Scale-IV-Translated in Japanese Parent Version: Investigator Administered and Scored (ADHDRS-IV-J:I) Total Score
Total Score 3 Years (n=105)
|
-20.0 Units on a scale
Standard Deviation 9.2
|
|
Change From Baseline at Various Timepoints in Attention Deficit Hyperactivity Disorder Rating Scale-IV-Translated in Japanese Parent Version: Investigator Administered and Scored (ADHDRS-IV-J:I) Total Score
Total Score 4 Years (n=62)
|
-20.1 Units on a scale
Standard Deviation 10.5
|
SECONDARY outcome
Timeframe: Baseline, 6 Months, 12 Months, 2 Years, 3 Years, 4 YearsPopulation: Full Analysis Set: Participants who met Study LYBC criteria, took 1 dose of drug, had a baseline/post-baseline measurement. Changes from baseline used LOCF approach. Baseline was the last non-missing measurement before taking atomoxetine (either LYDA Week 0 or LYBC Week 2). Endpoint was the last non-missing measurement in each assessment period.
Measures severity of the participant's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).
Outcome measures
| Measure |
Atomoxetine
n=228 Participants
0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
|
|---|---|
|
Change From Baseline at Various Timepoints in the Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S)
6 Months
|
-1.1 Units on a scale
Standard Deviation 1.1
|
|
Change From Baseline at Various Timepoints in the Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S)
12 Months
|
-1.3 Units on a scale
Standard Deviation 1.1
|
|
Change From Baseline at Various Timepoints in the Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S)
2 Years
|
-1.4 Units on a scale
Standard Deviation 1.0
|
|
Change From Baseline at Various Timepoints in the Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S)
3 Years
|
-1.6 Units on a scale
Standard Deviation 1.0
|
|
Change From Baseline at Various Timepoints in the Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S)
4 Years
|
-1.8 Units on a scale
Standard Deviation 1.1
|
SECONDARY outcome
Timeframe: Over 1 yearPopulation: Full Analysis Set: Participants who met Study LYBC criteria, took 1 dose of drug, had a baseline/post-baseline measurement. Changes from baseline used LOCF approach. Baseline was the last non-missing measurement before taking atomoxetine (either LYDA Week 0 or LYBC Week 2). Endpoint was the last non-missing measurement in each assessment period.
Participants were categorized as either extensive metabolizers (EM) or poor metabolizers (PM). CYP2D6 is the primary atomoxetine metabolizing enzyme. The CYP2D6 genotype were analysed by testing the \*2, \*3, \*4, \*5, \*6, \*7, \*8, and \*10 alleles. Metabolizer status was determined by focusing on the normal(wild type, \*2), decreased(\*10), and defective allele(\*3, \*4, \*5, \*6, \*7, or \*8). PM were assigned to the patients had two defective alleles in any combination of \*3, \*4, \*5, \*6, \*7, or \*8 alleles. EM was all except for PM.
Outcome measures
| Measure |
Atomoxetine
n=228 Participants
0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
|
|---|---|
|
Cytochrome P450 2D6 (CYP2D6) Phenotype Status
Extensive Metabolizer
|
225 Participants
|
|
Cytochrome P450 2D6 (CYP2D6) Phenotype Status
Poor Metabolizer
|
3 Participants
|
Adverse Events
Atomoxetine
Serious events: 6 serious events
Other events: 222 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Atomoxetine
n=228 participants at risk
0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
|
|---|---|
|
Endocrine disorders
Thyroiditis
|
0.44%
1/228 • Number of events 1
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.44%
1/228 • Number of events 1
|
|
Infections and infestations
Pneumonia mycoplasmal
|
0.44%
1/228 • Number of events 1
|
|
Injury, poisoning and procedural complications
Eye injury
|
0.44%
1/228 • Number of events 1
|
|
Psychiatric disorders
Schizophrenia
|
0.44%
1/228 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.44%
1/228 • Number of events 1
|
Other adverse events
| Measure |
Atomoxetine
n=228 participants at risk
0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
|
|---|---|
|
Eye disorders
Conjunctivitis allergic
|
5.7%
13/228 • Number of events 17
|
|
Eye disorders
Myopia
|
5.3%
12/228 • Number of events 13
|
|
Gastrointestinal disorders
Abdominal pain
|
23.2%
53/228 • Number of events 106
|
|
Gastrointestinal disorders
Constipation
|
7.5%
17/228 • Number of events 25
|
|
Gastrointestinal disorders
Dental caries
|
10.1%
23/228 • Number of events 24
|
|
Gastrointestinal disorders
Diarrhoea
|
18.4%
42/228 • Number of events 58
|
|
Gastrointestinal disorders
Nausea
|
12.3%
28/228 • Number of events 47
|
|
Gastrointestinal disorders
Stomatitis
|
8.8%
20/228 • Number of events 27
|
|
Gastrointestinal disorders
Toothache
|
5.3%
12/228 • Number of events 12
|
|
Gastrointestinal disorders
Vomiting
|
12.7%
29/228 • Number of events 45
|
|
General disorders
Malaise
|
6.1%
14/228 • Number of events 20
|
|
General disorders
Pyrexia
|
14.9%
34/228 • Number of events 43
|
|
Infections and infestations
Bronchitis
|
10.1%
23/228 • Number of events 39
|
|
Infections and infestations
Gastroenteritis
|
15.8%
36/228 • Number of events 53
|
|
Infections and infestations
Gastroenteritis viral
|
7.9%
18/228 • Number of events 25
|
|
Infections and infestations
Impetigo
|
6.6%
15/228 • Number of events 17
|
|
Infections and infestations
Influenza
|
24.1%
55/228 • Number of events 62
|
|
Infections and infestations
Nasopharyngitis
|
55.7%
127/228 • Number of events 420
|
|
Infections and infestations
Otitis media
|
5.3%
12/228 • Number of events 14
|
|
Infections and infestations
Pharyngitis
|
11.4%
26/228 • Number of events 46
|
|
Infections and infestations
Rhinitis
|
7.5%
17/228 • Number of events 31
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
7.9%
18/228 • Number of events 41
|
|
Injury, poisoning and procedural complications
Contusion
|
13.2%
30/228 • Number of events 51
|
|
Injury, poisoning and procedural complications
Excoriation
|
7.5%
17/228 • Number of events 30
|
|
Injury, poisoning and procedural complications
Fall
|
7.9%
18/228 • Number of events 26
|
|
Injury, poisoning and procedural complications
Joint sprain
|
9.6%
22/228 • Number of events 30
|
|
Metabolism and nutrition disorders
Decreased appetite
|
13.2%
30/228 • Number of events 36
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
5.7%
13/228 • Number of events 17
|
|
Nervous system disorders
Headache
|
29.4%
67/228 • Number of events 173
|
|
Nervous system disorders
Somnolence
|
14.9%
34/228 • Number of events 37
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.6%
22/228 • Number of events 27
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.6%
22/228 • Number of events 55
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.3%
12/228 • Number of events 14
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
9.6%
22/228 • Number of events 30
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
21.5%
49/228 • Number of events 139
|
|
Skin and subcutaneous tissue disorders
Eczema
|
9.2%
21/228 • Number of events 29
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
5.3%
12/228 • Number of events 24
|
|
Surgical and medical procedures
Tooth extraction
|
6.1%
14/228 • Number of events 22
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60