Attention Deficit Hyperactivity Disorder
Conditions
Brief summary
The study is long-term extension study to evaluate long-term safety and efficacy of Atomoxetine in Japanese pediatric patients with Attention-Deficit/Hyperactivity Disorder (AD/HD).
Interventions
DRUGAtomoxetine hydrochloride
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
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patients who met all of the disease diagnostic and study criteria at Visit 2 of previous placebo-controlled study, completed the study * Patients wish to enter into this study
Exclusion criteria
* Patients whose families anticipate a move outside the geographic range of the investigative site, or who plan extended travel inconsistent with the recommended visit interval
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events for Long Term Safety and Tolerability | Baseline through 4 years | Details on the actual adverse events are presented in the Reported Adverse Events Section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, 6 Months, 12 Months, 2 Years, 3 Years, 4 Years | 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. |
| Change From Baseline at Various Timepoints in the Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S) | Baseline, 6 Months, 12 Months, 2 Years, 3 Years, 4 Years | Measures severity of the participant's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients). |
| Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Over 1 year | 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. |
Countries
Japan
Participant flow
Recruitment details
This ongoing study is being conducted as a follow-up investigation of ADHD pediatric patients who completed Study LYBC (NCT00191295).
Participants by arm
| Arm | Count |
|---|---|
| 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 | 228 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 16 |
| Overall Study | Entry Criteria Exclusion | 3 |
| Overall Study | Lack of Efficacy | 15 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 11 |
| Overall Study | Protocol Violation | 18 |
| Overall Study | Withdrawal by Subject | 96 |
Baseline characteristics
| Characteristic | Atomoxetine |
|---|---|
| ADHD Rating Scale-IV-Translated in Japanese Parent Version: Investigator Administered/Scored | 22.23 Units on a scale STANDARD_DEVIATION 10.42 |
| Age at Onset of ADHD 0 Years | 1 Participants |
| Age at Onset of ADHD 1 Years | 17 Participants |
| Age at Onset of ADHD 2 Years | 25 Participants |
| Age at Onset of ADHD 3 Years | 49 Participants |
| Age at Onset of ADHD 4 Years | 45 Participants |
| Age at Onset of ADHD 5 Years | 47 Participants |
| Age at Onset of ADHD 6 Years | 40 Participants |
| Age at Onset of ADHD 7 Years | 4 Participants |
| Age Continuous | 10.69 years STANDARD_DEVIATION 2.48 |
| Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S) | 4.00 Units on a scale STANDARD_DEVIATION 1.04 |
| Duration of ADHD 10 Years | 11 Participants |
| Duration of ADHD 11 Years | 4 Participants |
| Duration of ADHD 12 Years | 7 Participants |
| Duration of ADHD 13 Years | 3 Participants |
| Duration of ADHD 14 Years | 3 Participants |
| Duration of ADHD 1 Years | 6 Participants |
| Duration of ADHD 2 Years | 8 Participants |
| Duration of ADHD 3 Years | 30 Participants |
| Duration of ADHD 4 Years | 24 Participants |
| Duration of ADHD 5 Years | 32 Participants |
| Duration of ADHD 6 Years | 26 Participants |
| Duration of ADHD 7 Years | 31 Participants |
| Duration of ADHD 8 Years | 21 Participants |
| Duration of ADHD 9 Years | 22 Participants |
| Duration of ADHD | 6.25 Years STANDARD_DEVIATION 2.85 |
| Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL Conduct Disorder | 2 Participants with Disorder Presently |
| Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL Generalized Anxiety Disorder | 1 Participants with Disorder Presently |
| Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL Obsessive Compulsive Disorder | 1 Participants with Disorder Presently |
| Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL Oppositional Defiant Disorder | 32 Participants with Disorder Presently |
| Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL Specific Phobia | 3 Participants with Disorder Presently |
| Mean Age at Onset of Attention Deficit Hyperactivity Disorder (ADHD) | 3.93 Years STANDARD_DEVIATION 1.57 |
| Race/Ethnicity, Customized East Asian | 228 Participants |
| Region of Enrollment Japan | 228 participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 195 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 222 / 228 |
| serious Total, serious adverse events | 6 / 228 |
Outcome results
Primary
Number of Participants With Adverse Events for Long Term Safety and Tolerability
Details on the actual adverse events are presented in the Reported Adverse Events Section.
Time frame: Baseline through 4 years
Population: All patients who took at least one dose of study medication were included in the analyses of safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Number of Participants With Adverse Events for Long Term Safety and Tolerability | Serious Adverse Events | 6 Participants |
| Atomoxetine | Number of Participants With Adverse Events for Long Term Safety and Tolerability | All Other Nonserious Adverse Events | 222 Participants |
Secondary
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
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.
Time frame: Baseline, 6 Months, 12 Months, 2 Years, 3 Years, 4 Years
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | 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 |
| Atomoxetine | 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 |
| Atomoxetine | 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 |
| Atomoxetine | 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 |
| Atomoxetine | 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 |
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
Secondary
Change From Baseline at Various Timepoints in the Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S)
Measures severity of the participant's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).
Time frame: Baseline, 6 Months, 12 Months, 2 Years, 3 Years, 4 Years
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | 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 |
| Atomoxetine | 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 |
| Atomoxetine | 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 |
| Atomoxetine | 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 |
| Atomoxetine | 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 |
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
Secondary
Cytochrome P450 2D6 (CYP2D6) Phenotype Status
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.
Time frame: Over 1 year
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Extensive Metabolizer | 225 Participants |
| Atomoxetine | Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Poor Metabolizer | 3 Participants |