Long-Term, Open Label Atomoxetine Study

Study Overview
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Brief Summary
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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.

Official Title
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Long-Term, Open Label Safety Study of Atomoxetine Hydrochloride in Patients, 6 Years and Older With Attention-Deficit/Hyperactivity Disorder

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: atomoxetine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atomoxetine<br>Atomoxetine-naive patients will have an acute titration to a stable dose, atomoxetine experienced patients whose therapy has been interrupted with be rapidly titrated to their previously established stable dose, and atomoxetine patients on a known stable dose may continue treatment at that dose. | Drug: atomoxetine<br>* 0.5-1.8 mg/kg/day, by mouth (PO), for up to 5 years<br>* Other names: Strattera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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%. | Baseline through 5 years | 
| 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 | 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. | baseline, 5 years | 
| 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. | baseline, 5 years | 
| Change From Baseline to 5 Year Endpoint in Heart Rate | Patients were assessed for changes in heart rate using electrocardiogram. | baseline, 5 years | 
| 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. | baseline through 5 years | 
| 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. | baseline through 5 years | 
| 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) | baseline through 5 years | 
| 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: age<11.0 (female) and age<12 (male) 11=<age<12 (female) or 12<=age<13 (male) 12=<age<15 (female) or 13=<age<15 (male) age>=15 (female and male) | 1 year through 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline, 5 years | 
| 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). | baseline, 5 years | 
| 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. | baseline, 5 years | 
| 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. | baseline, 5 years |