Attention Deficit Hyperactivity Disorder
Conditions
Keywords
ADHD
Brief summary
The purpose of this study is to assess the efficacy, the quality of life, and the safety of multiple dosing atomoxetine in Asian adult subjects with attention deficit/hyperactivity disorder (ADHD).
Detailed description
The treatment will be initiated at the lowest dosage 40 milligrams per day (mg/day), and it will be titrated up to 80 mg/day. Patients who are unable to tolerate a dose of at least 80 mg/day through the end of this study will be discontinued. The dosage will be titrated up to a maximum of 120 mg/day.
Interventions
DRUGAtomoxetine
40-120 milligrams (mg) taken by mouth, once daily for 10 weeks.
DRUGPlacebo
Taken by mouth, once daily for 10 weeks.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for current attention deficit/hyperactivity disorder (ADHD) as well as criteria for a historical diagnosis of ADHD during childhood, both assessed by the Conners' Adult Attention-Deficit/Hyperactivity Disorder Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition at screening * Patients must have a score of 2 or greater on at least 6 items of either the inattentive or hyperactive/impulsive core subscales at randomization or screening on the rated Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-item total ADHD symptom score. In addition, their total score on the 18-item total ADHD symptom score must be 20 or greater. * Patients must have a Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder-Severity score of 4 (moderate symptoms) or greater. * Patients must have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests, required by the protocol. * Patients must possess an educational level and degree of understanding of the language of their country that enables them to communicate suitably with the investigator and study coordinator. * Patients must be able to swallow capsules.
Exclusion criteria
* Patients who meet full DSM-IV-TR diagnostic criteria for any history of bipolar disorder or any history of schizophrenia and other psychotic disorders, or patients who had received injectable sustained-release neuroleptics. * Patients with depressive disorder who also have a total score of 12 or greater on the Hamilton Depression Rating Scale-17 items at randomization. Patients who have both a current or past history of major depression and received any anti-depression drug therapy within 6 months of screening. * Patients who meet DSM-IV-TR diagnostic criteria for current anxiety disorder and also patients who require anti-anxiety drug therapy, except for those taking benzodiazepine analogs for anxiety, which need to be limited. * Patients who have been diagnosed (DSM-IV-TR) with a pervasive developmental disorder. * Patients who, in the opinion of the investigator, are at serious suicidal risk or serious risk of harming others, or whose score for Item 11 on the Hamilton Depression Rating Scale-17 items is equal or more than 2 at randomization or screening. * Patients who have received atomoxetine in a prior clinical study. * Patients with significant medical conditions that are likely to become unstable during the trial or would likely be destabilized by treatment with atomoxetine. * Patients with a history of allergy to atomoxetine, severe allergies to more than 1 class of medications, or multiple adverse drug reactions. * Patients who have received treatment within the past 30 days with a drug that has not received regulatory approval for any indication at the time the informed consent document is obtained.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score up to 10 Weeks | Baseline, up to 10 weeks | CAARS-Inv:SV is a scale that assesses symptom severity over past week. Total ADHD symptom score consisted of 18 items (sum of inattention \[9 items, range: 0-27\] and hyperactivity-impulsivity \[9 items, range: 0-27\] subscales) using a 4-point scale (0=not at all/never to 3=very much/very frequently) for total score range of 0 to 54. Higher scores indicate greater impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score up to 10 Weeks | Baseline, up to 10 weeks | The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score is self-reported using a visual analogue scale marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state. |
| The Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score at 10 Weeks | 10 weeks | CAARS-Inv:SV assesses symptom severity over past week. Total ADHD symptom score comprises 18 items (sum of inattention \[9 items, range: 0-27\] and hyperactivity-impulsivity \[9 items, range: 0-27\] subscales) using a 4-point scale (0=not at all/never to 3=very much/very frequently). Total score range: 0 to 54. Higher scores=greater impairment. Least Squares Mean Value based on mixed model repeated measures analysis with term for baseline, country, visit, treatment, and treatment\*visit. Baseline included as a covariate; thus, treatment difference in observed value is same as change from baseline. |
| The Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Self Report: Screening Version (CAARS-S:SV) 18 Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score at 10 Weeks | 10 weeks | Participant assessment of symptom severity over past week. Total ADHD symptom score comprises 18 items (sum of inattention \[9 items, range: 0-27\] and hyperactivity-impulsivity \[9 items, range: 0-27\] subscales) using 4-point scale (0=not at all/never to 3=very much/very frequently). Total score range: 0 to 54. Higher scores=greater impairment. Least Squares Mean Value based on mixed model repeated measures analysis with term for baseline, country, visit, treatment, and treatment\*visit. Baseline included as covariate; thus, treatment difference in observed value is same as change from baseline. |
| Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Self Report (BRIEF-A:Self Report) Score up to 10 Weeks | Baseline, up to 10 weeks | A 75-item standardized self-reported measure comprised of 3 subscales. Each item is rated on a 3-point Likert scale (1=behavior never observed to 3=behavior often observed). Behavioral regulation subscale measures one's control over behavior (30-90 total score). Metacognition subscale assesses systematic problem-solving ability while sustaining these task-completion efforts in active working memory (40-120 total score). Global executive composite (GEC) subscale rates participant's GEC in everyday environment (75- 225 total score). Higher subscale ratings=greater perceived impairment. |
| Change From Baseline in the Adult Attention-Deficit/Hyperactivity Disorder Quality of Life-29 (AAQoL) Scores up to 10 Weeks | Baseline, up to 10 weeks | Participant-reported outcome measure used to examine disease-specific functional impairments and QoL for adults with ADHD. The domains include work functioning, family relationships, social functioning, activities of daily living (that is, driving, managing finances), and psychological adaptation (that is, life satisfaction and self-esteem). Individual items scored on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). Range of scores for this subscale is 0 to 100. Consistent with the majority of existing QoL measures, higher scores on AAQoL-29 indicate better functioning. |
| Change From Baseline in the Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) up to 10 Weeks | Baseline, up to 10 weeks | The CGI-ADHD-S is a single-item clinician rating of the clinician's assessment of the overall severity of the participant's ADHD symptoms in relation to the clinician's total experience with ADHD participants. Measures severity of the participant's overall severity of ADHD symptoms (1=normal, not at all ill to 7=among the most extremely ill participants). |
| Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) up to 10 Weeks | Up to 10 weeks | The CGI-ADHD-I is a single-item clinician rating of the clinician's assessment of the participant's improvement in ADHD symptoms in relation to the clinician's total experience with ADHD participants. Measures total improvement (or worsening) of a participant's ADHD symptoms from the beginning of treatment (1=very much improved to 7=very much worsened). |
| Change From Baseline in the Hamilton Anxiety Rating Scale-14 Items (HAMA-14) up to 10 Weeks | Baseline, up to 10 weeks | Clinician-administered rating scale that assesses severity of anxiety and its improvement (or change) during course of treatment (Hamilton 1959; Riskind et al. 1987). Scale consists of 14 items that provide an overall measure of general anxiety, including psychic anxiety and somatic anxiety. Investigator talked to participant about participant's symptoms over previous week before study visit. Each item is rated on a 5-point scale of 0 (absent) to 4 (very severe). Total score=sum of 14 items and ranges from 0 (normal) to 56 (severe). Higher scores indicate a greater degree of symptom severity. |
| Change From Baseline in the Hamilton Depression Rating Scale-17 Items (HAMD-17 Total) up to 10 Weeks | Baseline, up to 10 weeks | The HAMD-17 was used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present) to 4 (very severe) or a 3-point scale of 0 (not present) to 2 (marked). Higher scores indicate greater symptom severity. The total score is the sum of the scores from HAMD-17 Items 1 through 17. The total score may range from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate a greater degree of symptom severity. |
| Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Informant (BRIEF-A: Informant) Score up to 10 Weeks | Baseline, up to 10 weeks | Third-party observer of participant completes 75-item scale. Comprised of 3 subscales. Each item rated on 3-point Likert scale (1=behavior never observed to 3=behavior often observed). Behavioral regulation subscale measures one's control over behavior (30-90 total score). Metacognition subscale assesses systematic problem-solving ability while sustaining these task-completion efforts in active working memory (40-120 total score). Global executive composite (GEC) subscale rates participant's GEC in everyday environment (75-225 total score). Higher subscale ratings=greater perceived impairment. |
Countries
Japan, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine Treatment was started at 40 milligrams (mg) taken by mouth, once daily. The treatment period was 10 weeks, during which the dosage was up-titrated to a maximum of 120 mg by mouth, once daily. | 193 |
| Placebo Taken by mouth, once daily for 10 weeks. | 195 |
| Total | 388 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 3 |
| Overall Study | Entry Criteria Not Met | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 10 | 4 |
| Overall Study | Other | 2 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 6 | 8 |
| Overall Study | Sponsor Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 6 |
Baseline characteristics
| Characteristic | Atomoxetine | Placebo | Total |
|---|---|---|---|
| Age Continuous | 32.8 years STANDARD_DEVIATION 8.1 | 31.7 years STANDARD_DEVIATION 7.8 | 32.3 years STANDARD_DEVIATION 8 |
| Attention-Deficit/Hyperactivity Disorder (ADHD) Subtype Current Combined | 93 participants | 96 participants | 189 participants |
| Attention-Deficit/Hyperactivity Disorder (ADHD) Subtype Current Hyperactive/Impulsive | 4 participants | 4 participants | 8 participants |
| Attention-Deficit/Hyperactivity Disorder (ADHD) Subtype Current Inattentive | 96 participants | 95 participants | 191 participants |
| Conners' Adult Attention-Deficit Hyperactivity/Disorder Rating Scale-Investigator Rated: Screening V | 33.2 units on a scale STANDARD_DEVIATION 7.7 | 33.9 units on a scale STANDARD_DEVIATION 7.5 | 33.6 units on a scale STANDARD_DEVIATION 7.6 |
| Current Major Depressive Episode Status Major Depressive Episode - No | 189 participants | 195 participants | 384 participants |
| Current Major Depressive Episode Status Major Depressive Episode - Yes | 4 participants | 0 participants | 4 participants |
| Current Major Depressive Episode with Melancholic Features Status Current Major Depressive Episode with - No | 191 participants | 195 participants | 386 participants |
| Current Major Depressive Episode with Melancholic Features Status Current Major Depressive Episode with - Yes | 2 participants | 0 participants | 2 participants |
| Current Social Phobia (Social Anxiety Disorder [SAD]) Status Current Social Phobia (SAD) - No | 190 participants | 191 participants | 381 participants |
| Current Social Phobia (Social Anxiety Disorder [SAD]) Status Current Social Phobia (SAD) - Yes | 3 participants | 4 participants | 7 participants |
| Number of Participants with the Cytochrome P450 2D6 (CYP2D6) Genotype Extensive metabolizer (EM) | 40 participants | 45 participants | 85 participants |
| Number of Participants with the Cytochrome P450 2D6 (CYP2D6) Genotype Intermediate metabolizer (IM) | 137 participants | 137 participants | 274 participants |
| Number of Participants with the Cytochrome P450 2D6 (CYP2D6) Genotype Poor metabolizer (PM) | 0 participants | 0 participants | 0 participants |
| Number of Participants with the Cytochrome P450 2D6 (CYP2D6) Genotype Ultra-rapid metabolizer (UM) | 4 participants | 2 participants | 6 participants |
| Obsessive-Compulsive Disorder (OCD) Status Current OCD - No | 192 participants | 193 participants | 385 participants |
| Obsessive-Compulsive Disorder (OCD) Status Current OCD - Yes | 1 participants | 2 participants | 3 participants |
| Prior Stimulant Exposure Status Prior Stimulant Exposure - No | 150 participants | 153 participants | 303 participants |
| Prior Stimulant Exposure Status Prior Stimulant Exposure - Yes | 43 participants | 42 participants | 85 participants |
| Race/Ethnicity, Customized Asian | 193 participants | 195 participants | 388 participants |
| Recurrent Major Depressive Episode Status Recurrent Major Depressive Episode - No | 192 participants | 195 participants | 387 participants |
| Recurrent Major Depressive Episode Status Recurrent Major Depressive Episode - Yes | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Japan | 123 participants | 124 participants | 247 participants |
| Region of Enrollment Korea, Republic of | 36 participants | 37 participants | 73 participants |
| Region of Enrollment Taiwan | 34 participants | 34 participants | 68 participants |
| Sex: Female, Male Female | 103 Participants | 100 Participants | 203 Participants |
| Sex: Female, Male Male | 90 Participants | 95 Participants | 185 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 156 / 193 | 104 / 195 |
| serious Total, serious adverse events | 1 / 193 | 2 / 195 |
Outcome results
Primary
Change From Baseline in the Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score up to 10 Weeks
CAARS-Inv:SV is a scale that assesses symptom severity over past week. Total ADHD symptom score consisted of 18 items (sum of inattention \[9 items, range: 0-27\] and hyperactivity-impulsivity \[9 items, range: 0-27\] subscales) using a 4-point scale (0=not at all/never to 3=very much/very frequently) for total score range of 0 to 54. Higher scores indicate greater impairment.
Time frame: Baseline, up to 10 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline CAARS-Inv:SV result within each treatment group, last observation carried forward (LOCF) were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in the Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score up to 10 Weeks | -14.3 units on a scale | Standard Deviation 10.4 |
| Placebo | Change From Baseline in the Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score up to 10 Weeks | -8.8 units on a scale | Standard Deviation 9.6 |
p-value: <0.00195% CI: [-7.66, -3.91]ANCOVA
Secondary
Change From Baseline in the Adult Attention-Deficit/Hyperactivity Disorder Quality of Life-29 (AAQoL) Scores up to 10 Weeks
Participant-reported outcome measure used to examine disease-specific functional impairments and QoL for adults with ADHD. The domains include work functioning, family relationships, social functioning, activities of daily living (that is, driving, managing finances), and psychological adaptation (that is, life satisfaction and self-esteem). Individual items scored on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). Range of scores for this subscale is 0 to 100. Consistent with the majority of existing QoL measures, higher scores on AAQoL-29 indicate better functioning.
Time frame: Baseline, up to 10 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline AAQoL result within each treatment group, last observation carried forward (LOCF) were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in the Adult Attention-Deficit/Hyperactivity Disorder Quality of Life-29 (AAQoL) Scores up to 10 Weeks | 12.83 units on a scale | Standard Deviation 15.91 |
| Placebo | Change From Baseline in the Adult Attention-Deficit/Hyperactivity Disorder Quality of Life-29 (AAQoL) Scores up to 10 Weeks | 8.20 units on a scale | Standard Deviation 14.09 |
p-value: <0.00195% CI: [1.97, 7.56]ANCOVA
Secondary
Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Informant (BRIEF-A: Informant) Score up to 10 Weeks
Third-party observer of participant completes 75-item scale. Comprised of 3 subscales. Each item rated on 3-point Likert scale (1=behavior never observed to 3=behavior often observed). Behavioral regulation subscale measures one's control over behavior (30-90 total score). Metacognition subscale assesses systematic problem-solving ability while sustaining these task-completion efforts in active working memory (40-120 total score). Global executive composite (GEC) subscale rates participant's GEC in everyday environment (75-225 total score). Higher subscale ratings=greater perceived impairment.
Time frame: Baseline, up to 10 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline BRIEF-A result within each treatment group, last observation carried forward (LOCF) were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Informant (BRIEF-A: Informant) Score up to 10 Weeks | Raw Behavioral Regulation Index Score (N=126, 128) | -5.8 units on a scale | Standard Deviation 10.7 |
| Atomoxetine | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Informant (BRIEF-A: Informant) Score up to 10 Weeks | Raw Metacognition Index (MI) Score | -7.3 units on a scale | Standard Deviation 13.6 |
| Atomoxetine | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Informant (BRIEF-A: Informant) Score up to 10 Weeks | Raw Global Executive Composite Score (N=123, 128) | -13.2 units on a scale | Standard Deviation 22.7 |
| Placebo | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Informant (BRIEF-A: Informant) Score up to 10 Weeks | Raw Behavioral Regulation Index Score (N=126, 128) | -5.0 units on a scale | Standard Deviation 10.1 |
| Placebo | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Informant (BRIEF-A: Informant) Score up to 10 Weeks | Raw Metacognition Index (MI) Score | -7.3 units on a scale | Standard Deviation 12.8 |
| Placebo | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Informant (BRIEF-A: Informant) Score up to 10 Weeks | Raw Global Executive Composite Score (N=123, 128) | -12.4 units on a scale | Standard Deviation 21.6 |
p-value: 0.09295% CI: [-4.18, 0.32]ANCOVA
p-value: 0.27295% CI: [-4.52, 1.28]ANCOVA
p-value: 0.15395% CI: [-8.43, 1.32]ANCOVA
Secondary
Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Self Report (BRIEF-A:Self Report) Score up to 10 Weeks
A 75-item standardized self-reported measure comprised of 3 subscales. Each item is rated on a 3-point Likert scale (1=behavior never observed to 3=behavior often observed). Behavioral regulation subscale measures one's control over behavior (30-90 total score). Metacognition subscale assesses systematic problem-solving ability while sustaining these task-completion efforts in active working memory (40-120 total score). Global executive composite (GEC) subscale rates participant's GEC in everyday environment (75- 225 total score). Higher subscale ratings=greater perceived impairment.
Time frame: Baseline, up to 10 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline BRIEF-A result within each treatment group, last observation carried forward (LOCF) were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Self Report (BRIEF-A:Self Report) Score up to 10 Weeks | Raw Behavioral Regulation Index Score | -9.1 units on a scale | Standard Deviation 12.4 |
| Atomoxetine | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Self Report (BRIEF-A:Self Report) Score up to 10 Weeks | Raw Metacognition Index (MI) Score (N=177, 189) | -13.6 units on a scale | Standard Deviation 17.3 |
| Atomoxetine | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Self Report (BRIEF-A:Self Report) Score up to 10 Weeks | Raw Global Executive Composite Score (N=175, 189) | -22.6 units on a scale | Standard Deviation 28.8 |
| Placebo | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Self Report (BRIEF-A:Self Report) Score up to 10 Weeks | Raw Behavioral Regulation Index Score | -5.5 units on a scale | Standard Deviation 10.3 |
| Placebo | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Self Report (BRIEF-A:Self Report) Score up to 10 Weeks | Raw Metacognition Index (MI) Score (N=177, 189) | -7.5 units on a scale | Standard Deviation 13 |
| Placebo | Change From Baseline in the Behavior Rating Inventory of Executive Function-Adult Version: Self Report (BRIEF-A:Self Report) Score up to 10 Weeks | Raw Global Executive Composite Score (N=175, 189) | -13.0 units on a scale | Standard Deviation 22.1 |
p-value: 0.00195% CI: [-5.73, -1.45]ANCOVA
p-value: <0.00195% CI: [-9.28, -3.31]ANCOVA
p-value: <0.00195% CI: [-14.75, -4.78]ANCOVA
Secondary
Change From Baseline in the Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) up to 10 Weeks
The CGI-ADHD-S is a single-item clinician rating of the clinician's assessment of the overall severity of the participant's ADHD symptoms in relation to the clinician's total experience with ADHD participants. Measures severity of the participant's overall severity of ADHD symptoms (1=normal, not at all ill to 7=among the most extremely ill participants).
Time frame: Baseline, up to 10 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline CGI-ADHD-S result within each treatment group, last observation carried forward (LOCF) were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in the Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) up to 10 Weeks | -1.3 units on a scale | Standard Deviation 1.2 |
| Placebo | Change From Baseline in the Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) up to 10 Weeks | -0.8 units on a scale | Standard Deviation 1.1 |
p-value: <0.00195% CI: [-0.67, -0.27]ANCOVA
Secondary
Change From Baseline in the European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score up to 10 Weeks
The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score is self-reported using a visual analogue scale marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state.
Time frame: Baseline, up to 10 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline EQ-5D result within each treatment group, last observation carried forward (LOCF) were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in the European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score up to 10 Weeks | 1.4 units on a scale | Standard Deviation 20.3 |
| Placebo | Change From Baseline in the European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score up to 10 Weeks | 1.5 units on a scale | Standard Deviation 18.4 |
p-value: 0.28995% CI: [-5.2, 1.56]ANCOVA
Secondary
Change From Baseline in the Hamilton Anxiety Rating Scale-14 Items (HAMA-14) up to 10 Weeks
Clinician-administered rating scale that assesses severity of anxiety and its improvement (or change) during course of treatment (Hamilton 1959; Riskind et al. 1987). Scale consists of 14 items that provide an overall measure of general anxiety, including psychic anxiety and somatic anxiety. Investigator talked to participant about participant's symptoms over previous week before study visit. Each item is rated on a 5-point scale of 0 (absent) to 4 (very severe). Total score=sum of 14 items and ranges from 0 (normal) to 56 (severe). Higher scores indicate a greater degree of symptom severity.
Time frame: Baseline, up to 10 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline HAMA-14 result within each treatment group, last observation carried forward (LOCF) were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in the Hamilton Anxiety Rating Scale-14 Items (HAMA-14) up to 10 Weeks | -0.6 units on a scale | Standard Deviation 3.8 |
| Placebo | Change From Baseline in the Hamilton Anxiety Rating Scale-14 Items (HAMA-14) up to 10 Weeks | -0.7 units on a scale | Standard Deviation 3.6 |
p-value: 0.86995% CI: [-0.71, 0.6]ANCOVA
Secondary
Change From Baseline in the Hamilton Depression Rating Scale-17 Items (HAMD-17 Total) up to 10 Weeks
The HAMD-17 was used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present) to 4 (very severe) or a 3-point scale of 0 (not present) to 2 (marked). Higher scores indicate greater symptom severity. The total score is the sum of the scores from HAMD-17 Items 1 through 17. The total score may range from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate a greater degree of symptom severity.
Time frame: Baseline, up to 10 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline HAMD-17 result within each treatment group, last observation carried forward (LOCF) were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline in the Hamilton Depression Rating Scale-17 Items (HAMD-17 Total) up to 10 Weeks | -0.2 units on a scale | Standard Deviation 2.9 |
| Placebo | Change From Baseline in the Hamilton Depression Rating Scale-17 Items (HAMD-17 Total) up to 10 Weeks | -0.1 units on a scale | Standard Deviation 2.8 |
p-value: 0.8795% CI: [-0.59, 0.5]ANCOVA
Secondary
Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) up to 10 Weeks
The CGI-ADHD-I is a single-item clinician rating of the clinician's assessment of the participant's improvement in ADHD symptoms in relation to the clinician's total experience with ADHD participants. Measures total improvement (or worsening) of a participant's ADHD symptoms from the beginning of treatment (1=very much improved to 7=very much worsened).
Time frame: Up to 10 weeks
Population: All randomized participants with an endpoint CGI-ADHD-I value within each treatment group, last observation carried forward (LOCF) were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) up to 10 Weeks | 2.84 units on a scale | Standard Deviation 0.98 |
| Placebo | Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) up to 10 Weeks | 3.28 units on a scale | Standard Deviation 0.98 |
p-value: <0.001ANOVA
Secondary
The Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score at 10 Weeks
CAARS-Inv:SV assesses symptom severity over past week. Total ADHD symptom score comprises 18 items (sum of inattention \[9 items, range: 0-27\] and hyperactivity-impulsivity \[9 items, range: 0-27\] subscales) using a 4-point scale (0=not at all/never to 3=very much/very frequently). Total score range: 0 to 54. Higher scores=greater impairment. Least Squares Mean Value based on mixed model repeated measures analysis with term for baseline, country, visit, treatment, and treatment\*visit. Baseline included as a covariate; thus, treatment difference in observed value is same as change from baseline.
Time frame: 10 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline CAARS-Inv:SV result were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | The Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score at 10 Weeks | 17.24 units on a scale | Standard Error 0.74 |
| Placebo | The Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) 18-Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score at 10 Weeks | 23.42 units on a scale | Standard Error 0.73 |
p-value: <0.00195% CI: [-8.13, -4.22]Mixed Models Analysis
Secondary
The Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Self Report: Screening Version (CAARS-S:SV) 18 Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score at 10 Weeks
Participant assessment of symptom severity over past week. Total ADHD symptom score comprises 18 items (sum of inattention \[9 items, range: 0-27\] and hyperactivity-impulsivity \[9 items, range: 0-27\] subscales) using 4-point scale (0=not at all/never to 3=very much/very frequently). Total score range: 0 to 54. Higher scores=greater impairment. Least Squares Mean Value based on mixed model repeated measures analysis with term for baseline, country, visit, treatment, and treatment\*visit. Baseline included as covariate; thus, treatment difference in observed value is same as change from baseline.
Time frame: 10 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline CAARS-S:SV result were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | The Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Self Report: Screening Version (CAARS-S:SV) 18 Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score at 10 Weeks | 16.80 units on a scale | Standard Error 0.77 |
| Placebo | The Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Self Report: Screening Version (CAARS-S:SV) 18 Item Total Attention-Deficit/Hyperactivity Disorder (ADHD) Symptom Score at 10 Weeks | 22.97 units on a scale | Standard Error 0.75 |
p-value: <0.00195% CI: [-8.21, -4.14]Mixed Models Analysis