Attention Deficit Hyperactivity Disorder
Conditions
Brief summary
To learn about the safety and any side effects of atomoxetine when given to children and adolescents for about 5 years (long-term) and to learn whether atomoxetine can help children and adolescents with attention-deficit/hyperactivity disorder (ADHD) who take the drug for about 5 years (long-term). Study participants can be atomoxetine naive, atomoxetine experienced whose therapy has been interrupted or, atomoxetine experienced on a known stable dose.
Interventions
DRUGatomoxetine
0.5-1.8 mg/kg/day, by mouth (PO), for up to 5 years
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Must be at least 6 years old but less than 18 years old when enrolled in first atomoxetine study * Must meet the study criteria for ADHD * Must be willing to have blood drawn and to complete other test required for this study
Exclusion criteria
* allergic to more than 1 kind of medicine or have had multiple bad reactions to any drug * taking certain medicines that could interact with atomoxetine * plan to move too far away from a doctor participating in this study in the next 5 years * current or past history of any of the following: alcohol or drug abuse within the past 3 months, bipolar I or II disorder, high blood pressure, organic brain disease or seizures, psychosis, other disorders or conditions diagnosed by a doctor that might make you unsuitable to participate in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | 1 year through 5 years | Tanner Stage: I: no pubic hair at all (prepubertal Dominic state) II: small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females) III: hair becomes more coarse and curly, and begins to extend laterally IV: adult-like hair quality, extending across pubis but sparing medial thighs V: hair extends to medial surface of the thighs Age Groups: 1. age\<11.0 (female) and age\<12 (male) 2. 11=\<age\<12 (female) or 12\<=age\<13 (male) 3. 12=\<age\<15 (female) or 13=\<age\<15 (male) 4. age\>=15 (female and male) |
| Change From Baseline to 5 Year Endpoint in Heart Rate | baseline, 5 years | Patients were assessed for changes in heart rate using electrocardiogram. |
| Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) | baseline through 5 years | QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate. A corrected QT interval (QTc) has been corrected in order to aid interpretation. QTbz is the QT interval using Bazett's correction formula. QTfr is the QT interval using Fridericia's correction formula. QTdat is the QT interval using a data specific correction method for children. |
| Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | baseline through 5 years | QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate. A corrected QT interval (QTc) has been corrected in order to aid interpretation. QTbz is the QT interval using Bazett's correction formula. QTfr is the QT interval using Fridericia's correction formula. QTdat is the QT interval using a data specific correction method for children. For Males: Normal is \<430 ms, Borderline is \>=430 ms and \<450 ms, Prolonged is \>=450 ms. For Females: Normal is \<450 ms, Borderline is \>=450 ms and \<470 ms, Prolonged is \>=470 ms. |
| Number of Participants With Abnormal Laboratory Analytes During the Study | baseline through 5 years | Standard reference ranges from Covance Laboratories were used in the determination of abnormal high and low values based on age and gender, where appropriate. Aspartate aminotransferase (AST); serum glutamic oxaloacetic transaminase (SGOT); units/liter (U/L); alanine aminotransferase (ALT); serum glutamic pyruvic transaminase (SGPT); millimoles/liter (mmol/L); grams/liter (g/L); micromoles/liter (umol/L); millimoles/liter-iron (mmol/L-Fe); trillion/liter (TI/L)or 10\^12 units/liter; Giga/liter (GI/L)or 10\^9 units/liter; femtoliters (fL); urinalysis (UA) |
| Categorical Changes in Vital Signs (Blood Pressure [BP], Pulse, Weight, Temperature) During the Study | Baseline through 5 years | Vital signs were assesed categorically using the term high for BP, high and low for pulse and temperature, or decreased for weight. For BP, high was an increase to a value above the 95th percentile of the National Institute of Health (NIH) values. For pulse, high was an increase of at least 25 beats per minute to at least 110, and low was a decrease of at least 20 beats per minute to at most 65 beats per minute. For temperature, high was an increase of at least 1 to 37.7 and low was a decrease of at least 1.3 to at most 35.6. Decrease in weight was marked by a reduction of at least 3.5%. |
| Change From Baseline to 5 Year Endpoint in BP | baseline, 5 years | — |
| Change From Baseline to 5 Year Endpoint in Pulse | baseline, 5 years | — |
| Change From Baseline to 5 Year Endpoint in Body Weight | baseline, 5 years | — |
| Change From Baseline to 5 Year Endpoint in Height | baseline, 5 years | — |
| Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | baseline, 5 years | Patients were assessed for changes in weight, height, and BMI. BMI is an estimate of body fat based on body weight divided by height squared. |
| Change From Baseline to 5 Year Endpoint in Electrocardiogram (ECG) | baseline, 5 years | Patients were assessed for changes in ECG. The RR interval is the time duration between two consecutive R waves of the ECG. The QRS interval is the beginning of Q to the end of the S wave. The QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate. A corrected QT interval (QTc) has been corrected in order to aid interpretation. QTbz is the QT interval using Bazett's correction formula. QTfr is the QT interval using Fridericia's correction formula.QTdat is the QT interval using a data specific correction method for children. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 5 Year Endpoint in Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder-Severity (CGI-ADHD-S) Score | baseline, 5 years | Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients). |
| Change From Baseline to 5 Year Endpoint in Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Subscale Scores | baseline, 5 years | 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 5 Year Endpoint in the Stroop Word Color Test | baseline, 5 years | Only patients who took the Stroop Color Word Test in a previous atomoxetine study were required to complete the Stroop in this study. Stroop measures inhibition of dominant response and interference control. Patients were given tasks of recognition (colors), reading (where a word represents a color), and interference (reading words written in different colors). There were 100 items for each of the three categories and if they made it through 100 words with time remaining, they would repeat the list. Only a small number of patients had Stroop tests in this study, so no analysis was done. |
| Change From Baseline to 5 Year Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score and Subscale Scores | baseline, 5 years | Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of ADHD. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. Hyperactive/Impulsive and Inattention Subscales consisted of 9 items each, for total subscale score range of 0 to 27. ADHD Index Subscale consisted of 12 items, for total score range of 0 to 36. |
Countries
Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Norway, Puerto Rico, South Africa, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine Atomoxetine-naive patients will have an acute titration to a stable dose, atomoxetine experienced patients whose therapy has been interrupted will be rapidly titrated to their previously established stable dose, and atomoxetine patients on a known stable dose may continue treatment at that dose. | 1,553 |
| Total | 1,553 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 86 |
| Overall Study | Clinical relapse | 67 |
| Overall Study | Lack of efficacy | 204 |
| Overall Study | Lost to Follow-up | 232 |
| Overall Study | Patient Decision | 432 |
| Overall Study | Patient moved | 60 |
| Overall Study | Physician Decision | 84 |
| Overall Study | Protocol Violation | 123 |
| Overall Study | Satisfactory response | 80 |
| Overall Study | Sponsor's decision | 17 |
| Overall Study | Study Period III Completed | 103 |
| Overall Study | Study Period V Completed | 1 |
Baseline characteristics
| Characteristic | Atomoxetine |
|---|---|
| Age Continuous | 11.62 years STANDARD_DEVIATION 2.6 |
| Attention Deficit Hyperactive Disorder (ADHD) Subtype Combined | 1016 participants |
| Attention Deficit Hyperactive Disorder (ADHD) Subtype Hyperactive/Impulsive | 46 participants |
| Attention Deficit Hyperactive Disorder (ADHD) Subtype Inattentive | 413 participants |
| Attention Deficit Hyperactive Disorder (ADHD) Subtype Not Applicable | 72 participants |
| Attention Deficit Hyperactive Disorder (ADHD) Subtype Unknown | 6 participants |
| Height | 147.89 centimeters (cm) STANDARD_DEVIATION 15.72 |
| Race/Ethnicity, Customized African Descent | 98 participants |
| Race/Ethnicity, Customized Caucasian | 1317 participants |
| Race/Ethnicity, Customized East/ Southeast Asian | 9 participants |
| Race/Ethnicity, Customized Hispanic | 76 participants |
| Race/Ethnicity, Customized Other | 52 participants |
| Race/Ethnicity, Customized Western Asian | 1 participants |
| Region of Enrollment Australia | 22 participants |
| Region of Enrollment Belgium | 20 participants |
| Region of Enrollment Canada | 14 participants |
| Region of Enrollment France | 21 participants |
| Region of Enrollment Germany | 21 participants |
| Region of Enrollment Israel | 16 participants |
| Region of Enrollment Italy | 11 participants |
| Region of Enrollment Netherlands | 15 participants |
| Region of Enrollment Norway | 13 participants |
| Region of Enrollment Puerto Rico | 19 participants |
| Region of Enrollment South Africa | 19 participants |
| Region of Enrollment Spain | 23 participants |
| Region of Enrollment Sweden | 27 participants |
| Region of Enrollment United Kingdom | 24 participants |
| Region of Enrollment United States | 1288 participants |
| Sex: Female, Male Female | 338 Participants |
| Sex: Female, Male Male | 1215 Participants |
| Weight | 43.73 kilograms (kg) STANDARD_DEVIATION 16.03 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1,372 / 1,551 |
| serious Total, serious adverse events | 92 / 1,551 |
Outcome results
Primary
Categorical Changes in Vital Signs (Blood Pressure [BP], Pulse, Weight, Temperature) During the Study
Vital signs were assesed categorically using the term high for BP, high and low for pulse and temperature, or decreased for weight. For BP, high was an increase to a value above the 95th percentile of the National Institute of Health (NIH) values. For pulse, high was an increase of at least 25 beats per minute to at least 110, and low was a decrease of at least 20 beats per minute to at most 65 beats per minute. For temperature, high was an increase of at least 1 to 37.7 and low was a decrease of at least 1.3 to at most 35.6. Decrease in weight was marked by a reduction of at least 3.5%.
Time frame: Baseline through 5 years
Population: For each vital sign, the number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug. Number of subject analyzed for each vital sign is provided.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Categorical Changes in Vital Signs (Blood Pressure [BP], Pulse, Weight, Temperature) During the Study | Systolic BP High (N=1431) | 228 participants |
| Atomoxetine | Categorical Changes in Vital Signs (Blood Pressure [BP], Pulse, Weight, Temperature) During the Study | Diastolic BP High (N=1458) | 92 participants |
| Atomoxetine | Categorical Changes in Vital Signs (Blood Pressure [BP], Pulse, Weight, Temperature) During the Study | Pulse High (N=1528) | 19 participants |
| Atomoxetine | Categorical Changes in Vital Signs (Blood Pressure [BP], Pulse, Weight, Temperature) During the Study | Pulse Low (N=1528) | 39 participants |
| Atomoxetine | Categorical Changes in Vital Signs (Blood Pressure [BP], Pulse, Weight, Temperature) During the Study | Temperature High (N=1525) | 7 participants |
| Atomoxetine | Categorical Changes in Vital Signs (Blood Pressure [BP], Pulse, Weight, Temperature) During the Study | Temperature Low (N=1525) | 9 participants |
| Atomoxetine | Categorical Changes in Vital Signs (Blood Pressure [BP], Pulse, Weight, Temperature) During the Study | Weight Decrease (N=1526) | 61 participants |
Primary
Change From Baseline to 5 Year Endpoint in Body Weight
Time frame: baseline, 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Body Weight | 11.0 kilograms (kg) | Standard Deviation 11.66 |
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Primary
Change From Baseline to 5 Year Endpoint in BP
Time frame: baseline, 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 5 Year Endpoint in BP | Systolic BP | 4.7 millimeters of Mercury (mmHg) | Standard Deviation 11.56 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in BP | Diastolic BP | 1.3 millimeters of Mercury (mmHg) | Standard Deviation 9.04 |
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon sign-rank test
Primary
Change From Baseline to 5 Year Endpoint in Electrocardiogram (ECG)
Patients were assessed for changes in ECG. The RR interval is the time duration between two consecutive R waves of the ECG. The QRS interval is the beginning of Q to the end of the S wave. The QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate. A corrected QT interval (QTc) has been corrected in order to aid interpretation. QTbz is the QT interval using Bazett's correction formula. QTfr is the QT interval using Fridericia's correction formula.QTdat is the QT interval using a data specific correction method for children.
Time frame: baseline, 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Electrocardiogram (ECG) | RR Interval | 27.2 milliseconds (msec) | Standard Deviation 138.78 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Electrocardiogram (ECG) | QRS Interval | 2.6 milliseconds (msec) | Standard Deviation 7.19 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Electrocardiogram (ECG) | QT Bazett (bz) Correction | -1.7 milliseconds (msec) | Standard Deviation 17.85 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Electrocardiogram (ECG) | QT Data (dat) Correction | -0.2 milliseconds (msec) | Standard Deviation 15.43 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Electrocardiogram (ECG) | QT Fridericia (fr) Correction | 0.5 milliseconds (msec) | Standard Deviation 15.71 |
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: 0.31Wilcoxon signed-rank test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: 0.632Wilcoxon signed-rank test
Primary
Change From Baseline to 5 Year Endpoint in Heart Rate
Patients were assessed for changes in heart rate using electrocardiogram.
Time frame: baseline, 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Heart Rate | -2.5 beats per minute (bpm) | Standard Deviation 14.45 |
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Primary
Change From Baseline to 5 Year Endpoint in Height
Time frame: baseline, 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Height | 10.9 centimeters (cm) | Standard Deviation 10.41 |
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Primary
Change From Baseline to 5 Year Endpoint in Pulse
Time frame: baseline, 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Pulse | -1.5 beats per minute (bpm) | Standard Deviation 13.83 |
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Primary
Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile
Patients were assessed for changes in weight, height, and BMI. BMI is an estimate of body fat based on body weight divided by height squared.
Time frame: baseline, 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and 5 year endpoint measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | Weight (0 to 25th percentile) (N=46) | 18.93 percentiles | Standard Deviation 9.26 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | Weight (25th to 50th percentile) (N=58) | 14.90 percentiles | Standard Deviation 22.31 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | Weight (50th to 75th percentile) (N=50) | -1.33 percentiles | Standard Deviation 20.21 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | Weight (75th to 100th percentile) (N=97) | -6.68 percentiles | Standard Deviation 15.5 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | Height (0 to 25th percentile) (N=64) | 12.06 percentiles | Standard Deviation 21 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | Height (25th tp 50th percentile) (N=61) | 9.53 percentiles | Standard Deviation 21.76 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | Height (50th to 75th percentile) (N=55) | -6.28 percentiles | Standard Deviation 22.55 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | Height (75th to 100th percentile) (N=65) | -10.92 percentiles | Standard Deviation 20.31 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | BMI (0 to 25th percentile) (N=34) | 18.71 percentiles | Standard Deviation 24.76 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | BMI (25th to 50th percentile) (N=53) | 8.52 percentiles | Standard Deviation 28.11 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | BMI (50th to 75th percentile) (N=55) | -3.26 percentiles | Standard Deviation 25.69 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile | BMI (75th to 100th percentile) (N=101) | -7.94 percentiles | Standard Deviation 18.41 |
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: 0.644paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: 0.001paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: 0.044paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: 0.032paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: 0.351paired t-test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001paired t-test
Primary
Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group
Tanner Stage: I: no pubic hair at all (prepubertal Dominic state) II: small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females) III: hair becomes more coarse and curly, and begins to extend laterally IV: adult-like hair quality, extending across pubis but sparing medial thighs V: hair extends to medial surface of the thighs Age Groups: 1. age\<11.0 (female) and age\<12 (male) 2. 11=\<age\<12 (female) or 12\<=age\<13 (male) 3. 12=\<age\<15 (female) or 13=\<age\<15 (male) 4. age\>=15 (female and male)
Time frame: 1 year through 5 years
Population: The analysis population is defined as patients with at least two Tanner measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 1, Tanner I (N=2) | 1 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 4, Tanner II (N=55) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 1, Tanner I (N=7) | 2 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 1, Tanner II (N=7) | 2 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 1, Tanner III (N=7) | 2 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 1, Tanner IV (N=7) | 1 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 1, Tanner V (N=7) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 2, Tanner I (N=14) | 4 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 2, Tanner II (N=14) | 6 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 2, Tanner III (N=14) | 2 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 2, Tanner IV (N=14) | 2 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 2, Tanner V (N=14) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 3, Tanner I (N=37) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 3, Tanner II (N=37) | 2 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 3, Tanner III (N=37) | 13 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 3, Tanner IV (N=37) | 15 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 3, Tanner V (N=37) | 7 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 4, Tanner I (N=35) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 4, Tanner II (N=35) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 4, Tanner III (N=35) | 2 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 4, Tanner IV (N=35) | 11 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | First Tanner, Age Group 4, Tanner V (N=35) | 22 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 1, Tanner II (N=2) | 1 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 1, Tanner III (N=2) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 1, Tanner IV (N=2) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 1, Tanner V (N=2) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 2, Tanner I (N=4) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 2, Tanner II (N=4) | 1 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 2, Tanner III (N=4) | 2 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 2, Tanner IV (N=4) | 1 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 2, Tanner V (N=4) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 3, Tanner I (N=32) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 3, Tanner II (N=32) | 5 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 3, Tanner III (N=32) | 8 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 3, Tanner IV (N=32) | 14 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 3, Tanner V (N=32) | 5 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 4, Tanner I (N=55) | 0 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 4, Tanner III (N=55) | 3 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 4, Tanner IV (N=55) | 19 participants |
| Atomoxetine | Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group | Endpoint Tanner, Age Group 4, Tanner V (N=55) | 33 participants |
Primary
Number of Participants With Abnormal Laboratory Analytes During the Study
Standard reference ranges from Covance Laboratories were used in the determination of abnormal high and low values based on age and gender, where appropriate. Aspartate aminotransferase (AST); serum glutamic oxaloacetic transaminase (SGOT); units/liter (U/L); alanine aminotransferase (ALT); serum glutamic pyruvic transaminase (SGPT); millimoles/liter (mmol/L); grams/liter (g/L); micromoles/liter (umol/L); millimoles/liter-iron (mmol/L-Fe); trillion/liter (TI/L)or 10\^12 units/liter; Giga/liter (GI/L)or 10\^9 units/liter; femtoliters (fL); urinalysis (UA)
Time frame: baseline through 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | AST/SGOT (U/L) High (N=1484) | 27 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | AST/SGOT (U/L) Low (N=1484) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | ALT/SGPT (U/L) Low (N=1486) | 2 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | ALT/SGPT (U/L) High (N=1486) | 38 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Creatine Phosphokinase (U/L) Low (N=1485) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Creatine Phosphokinase (U/L) High (N=1485) | 57 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Alkaline Phosphatase (U/L) Low (N=1486) | 67 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Alkaline Phosphatase (U/L) High (N=1486) | 83 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Gamma Glutamyltransferase (U/L) Low (N=1486) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Gamma Glutamyltransferase (U/L) High (N=1486) | 17 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Urea Nitrogen (mmol/L) Low (N=1487) | 1 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Urea Nitrogen (mmol/L) High (N=1487) | 2 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Calcium (mmol/L) Low (N=1487) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Calcium (mmol/L) High (N=1487) | 117 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Inorganic Phosphorus (mmol/L) Low (N=1485) | 10 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Inorganic Phosphorus (mmol/L) High (N=1485) | 31 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Total Protein (g/L) Low (N=1487) | 2 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Total Protein (g/L) High (N=1487) | 5 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Albumin (g/L) Low (N=1487) | 1 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Albumin (g/L) High (N=1487) | 113 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Glucose, Non-Fasting/Random (mmol/L) Low (N=1486) | 20 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Glucose, Non-Fasting/Random (mmol/L) High (N=1486) | 1 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Uric Acid (umol/L) Low (N=1487) | 6 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Uric Acid (umol/L) High (N=1487) | 130 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Cholesterol (mmol/L) Low (N=1487) | 87 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Cholesterol (mmol/L) High (N=1487) | 72 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Creatinine (umol/L) Low (N=1487) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Creatinine (umol/L) High (N=1487) | 285 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Total Bilirubin (umol/L) Low (N=1458) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Total Bilirubin (umol/L) High (N=1458) | 38 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Hematocrit (1) Low (N=1482) | 24 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Hematocrit (1) High (N=1482) | 85 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Hemoglobin (mmL/L-Fe) Low (N=1482) | 14 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Hemoglobin (mmL/L-Fe) High (N=1482) | 30 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Erythrocyte Count (TI/L) Low (N=1482) | 8 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Erythrocyte Count (TI/L) High (N=1482) | 3 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Leukocyte Count (GI/L) Low (N=1482) | 63 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Leukocyte Count (GI/L) High (N=1482) | 8 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Bands (GI/L) Low (N=1482) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Bands (GI/L) High (N=1482) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Neutrophils, Segmented (GI/L) Low (N=1482) | 20 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Neutrophils, Segmented (GI/L) High (N=1482) | 23 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Lymphocytes (GI/L) Low (N=1482) | 6 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Lymphocytes (GI/L) High (N=1482) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Monocytes (GI/L) Low (N=1482) | 62 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Monocytes (GI/L) High (N=1482) | 12 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Eosinophils (GI/L) Low (N=1482) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Eosinophils (GI/L) High (N=1482) | 54 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Basophils (GI/L) Low (N=1482) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Basophils (GI/L) High (N=1482) | 3 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Mean Cell Volume (fL) Low (N=1482) | 26 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Mean Cell Volume (fL) High (N=1482) | 10 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Platelet Count (GI/L) Low (N=1479) | 1 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Platelet Count (GI/L) High (N=1479) | 63 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Sodium (mmol/L) Low (N=1486) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Sodium (mmol/L) High (N=1486) | 2 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Potassium (mmol/L) Low (N=1484) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Potassium (mmol/L) High (N=1484) | 8 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Chloride (mmol/L) Low (N=1486) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Chloride (mmol/L) High (N=1486) | 2 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Bicarbonate (mmol/L) Low (N=1486) | 7 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Bicarbonate (mmol/L) High (N=1486) | 6 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | UA-Specific Gravity (no units) Low (N=1486) | 39 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | UA-Specific Gravity (no units) High (N=1486) | 73 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Lymphocytes, Atypical (GI/L) Low (N=52) | 0 participants |
| Atomoxetine | Number of Participants With Abnormal Laboratory Analytes During the Study | Lymphocytes, Atypical (GI/L) High (N=52) | 52 participants |
Primary
Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase)
QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate. A corrected QT interval (QTc) has been corrected in order to aid interpretation. QTbz is the QT interval using Bazett's correction formula. QTfr is the QT interval using Fridericia's correction formula. QTdat is the QT interval using a data specific correction method for children.
Time frame: baseline through 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) | QTc (bz) Increase of at least 60 ms | 2 participants |
| Atomoxetine | Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) | QTc (bz) Increase to values >500 ms | 0 participants |
| Atomoxetine | Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) | QTc (dat) Increase of at least 30 ms | 50 participants |
| Atomoxetine | Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) | QTc (bz) Increase of at least 30 milliseconds (ms) | 68 participants |
| Atomoxetine | Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) | QTc (dat) Increase of at least 60 ms | 2 participants |
| Atomoxetine | Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) | QTc (dat) Increase to values >500 ms | 0 participants |
| Atomoxetine | Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) | QTc (fr) Increase of at least 30 ms | 56 participants |
| Atomoxetine | Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) | QTc (fr) Increase of at least 60 ms | 2 participants |
| Atomoxetine | Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) | QTc (fr) Increase to values >500 ms | 0 participants |
Primary
Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint)
QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate. A corrected QT interval (QTc) has been corrected in order to aid interpretation. QTbz is the QT interval using Bazett's correction formula. QTfr is the QT interval using Fridericia's correction formula. QTdat is the QT interval using a data specific correction method for children. For Males: Normal is \<430 ms, Borderline is \>=430 ms and \<450 ms, Prolonged is \>=450 ms. For Females: Normal is \<450 ms, Borderline is \>=450 ms and \<470 ms, Prolonged is \>=470 ms.
Time frame: baseline through 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (dat) Borderline Baseline/Prolonged Endpoint | 1 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (fr) Normal Baseline/Normal Endpoint | 1454 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (fr) Normal Baseline/Prolonged Endpoint | 2 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (fr) Prolonged Baseline/Prolonged Endpoint | 0 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (bz) Normal Baseline/Normal Endpoint | 1069 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (bz) Normal Baseline/Borderline Endpoint | 156 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (bz) Normal Baseline/Prolonged Endpoint | 11 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (bz) Borderline Baseline/Normal Endpoint | 180 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (bz) Borderline Baseline/Borderline Endpoint | 49 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (bz) Borderline Baseline/Prolonged Endpoint | 6 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (bz) Prolonged Baseline/Normal Endpoint | 6 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (bz) Prolonged Baseline/Borderline Endpoint | 5 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (bz) Prolonged Baseline/Prolonged Endpoint | 0 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (dat) Normal Baseline/Normal Endpoint | 1433 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (dat) Normal Baseline/Borderline Endpoint | 26 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (dat) Normal Baseline/Prolonged Endpoint | 1 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (dat) Borderline Baseline/Normal Endpoint | 16 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (dat) Borderline Baseline/Borderline Endpoint | 3 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (dat) Prolonged Baseline/Normal Endpoint | 2 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (dat) Prolonged Baseline/Borderline Endpoint | 0 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (dat) Prolonged Baseline/Prolonged Endpoint | 0 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (fr) Normal Baseline/Borderline Endpoint | 16 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (fr) Borderline Baseline/Normal Endpoint | 7 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (fr) Borderline Baseline/Borderline Endpoint | 0 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (fr) Borderline Baseline/Prolonged Endpoint | 1 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (fr) Prolonged Baseline/Normal Endpoint | 2 participants |
| Atomoxetine | Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) | QTc (fr) Prolonged Baseline/Borderline Endpoint | 0 participants |
Secondary
Change From Baseline to 5 Year Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score and Subscale Scores
Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of ADHD. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. Hyperactive/Impulsive and Inattention Subscales consisted of 9 items each, for total subscale score range of 0 to 27. ADHD Index Subscale consisted of 12 items, for total score range of 0 to 36.
Time frame: baseline, 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score and Subscale Scores | Total Score | 3.5 units on a scale | Standard Deviation 9.62 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score and Subscale Scores | Inattentive Subscale Score | 2.6 units on a scale | Standard Deviation 6 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score and Subscale Scores | Hyperactive Subscale Score | 0.9 units on a scale | Standard Deviation 4.73 |
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: p<0Wilcoxon signed-rank test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: p<0Wilcoxon signed-rank test
Secondary
Change From Baseline to 5 Year Endpoint in Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder-Severity (CGI-ADHD-S) Score
Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).
Time frame: baseline, 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder-Severity (CGI-ADHD-S) Score | 0.523 units on a scale | Standard Deviation 1.149 |
p-value: <0.001Wilcoxon signed-rank test
Secondary
Change From Baseline to 5 Year Endpoint in Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Subscale Scores
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: baseline, 5 years
Population: The number of participants analyzed was defined as all patients with a baseline and post-baseline measurement, except patients reported as not taking any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Subscale Scores | CPRS Hyperactive Subscale (n=1057) | 0.325 units on a scale | Standard Deviation 3.287 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Subscale Scores | CPRS ADHD Index Subscale (n=1056) | 2.411 units on a scale | Standard Deviation 7.785 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Subscale Scores | CPRS Cognitive Subscale (n=1056) | 1.500 units on a scale | Standard Deviation 4.777 |
| Atomoxetine | Change From Baseline to 5 Year Endpoint in Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Subscale Scores | CPRS Oppositional Subscale (n=1059) | 1.357 units on a scale | Standard Deviation 4.287 |
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: p<0Wilcoxon signed-rank test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: 0.026Wilcoxon signed-rank test
Comparison: Tested was the null hypothesis that there would be no statistically significant difference between baseline and endpoint.p-value: <0.001Wilcoxon signed-rank test
Secondary
Change From Baseline to 5 Year Endpoint in the Stroop Word Color Test
Only patients who took the Stroop Color Word Test in a previous atomoxetine study were required to complete the Stroop in this study. Stroop measures inhibition of dominant response and interference control. Patients were given tasks of recognition (colors), reading (where a word represents a color), and interference (reading words written in different colors). There were 100 items for each of the three categories and if they made it through 100 words with time remaining, they would repeat the list. Only a small number of patients had Stroop tests in this study, so no analysis was done.
Time frame: baseline, 5 years
Population: There were not enough participants with prior Stroop Word Color tests to analyze the data.