Atomoxetine Asian Study in Adult Subjects With Attention-Deficit/Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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The primary objective of this clinical study is to assess overall safety and tolerability as measured by discontinuation rate due to adverse events in doses up to 120 mg/day in relation to global clinical studies in adult subjects who meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV™) criteria for Attention-Deficit/Hyperactivity Disorder (ADHD).

Official Title
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An Open Study of Atomoxetine (LY139603) in Adult Subjects 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: at least 18 years of age meet Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID) diagnostic criteria for current ADHD as well as meeting criteria for a historical diagnosis of ADHD during childhood have a Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) score of 4 (moderate symptoms) or greater Exclusion Criteria: Patients who meet DSM-IV diagnostic criteria for current major depression and also patients who have total score of more than 12 on the 17-item Hamilton Depression Rating Scale (HAMD-17) at Visit 1 and Visit 2. Patients who have both a current or past history of major depression and have received any anti-depression drug therapy within 6 months of Visit 1. Patients who meet DSM-IV diagnostic criteria for have a current anxiety disorder and also require anti-anxiety drug therapy except for those taking benzodiazepines analogues for anxiety which need to be limited. Patients who have any history of bipolar disorder (DSM-IV) , any history of schizophrenia or any history of a psychotic disorder (DSM-IV) will be excluded from the study. Patients who have been diagnosed (DSM-IV) with a pervasive developmental disorder.

Ages Eligible for Study
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Minimum 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> | Drug: Atomoxetine<br>* Study drug is administered once daily in the morning. This study is designed with 4-step titration. At Day 1, study drug is started from 40 mg/day, and is increased to 80 mg/day on Day 7, 105 mg/day on Day 14, and 120 mg/day on Day 28. Total administration period is 8 weeks. The dosage is adjusted according to investigator's decision based on safety and tolerability.<br>* Other names: Strattera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Discontinuations Due to Adverse Events (AE) | The definition of a study adverse event was any unfavorable medical event, newly emerged or a deterioration of a preexisting condition, in other words any untoward medical occurrence in a patient administered a pharmaceutical product, without regard to the possibility of a causal relationship, that occurred after the visit for informed consent and up to the visit for completion of administration, or discontinuation. | Baseline to 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 8 Week Endpoint in Conners' Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Rating Scale-Investigator Rated:Screening Version (CAARS-Inv:SV) Total ADHD Symptom Score | Conners' Adult Attention-Deficit Hyperactivity Disorder (ADHD) Rating Scale-Investigator Rating:Screening Version. Total ADHD symptom score consisted of 18 items (sum of inattention and hyperactivity-impulsivity 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. | Baseline and 8 Weeks | 
| Change From Baseline to 8 Week Endpoint in Clinical Global Impressions-ADHD Severity (CGI-ADHD-S) | 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 and 8 Weeks | 
| Change From Baseline to 8 Week Endpoint in Conners' Adult ADHD Rating Scale-Self Rated:Screening Version (CAARS-S:SV) Total ADHD Symptom Score | Conners' Adult Attention-Deficit Hyperactivity Disorder (ADHD) Rating Scale-Self Rating:Screening Version. Total ADHD symptom score consisted of 18 items (sum of inattention and hyperactivity-impulsivity 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. | Baseline and 8 Weeks | 
| Change From Baseline to 8 Week Endpoint in 17-Item Hamilton Depression Rating Scale (HAMD-17) | The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). | Baseline and 8 Weeks | 
| Change From Baseline to 8 Week Endpoint in Hamilton Anxiety Rating Scale (HAMA-14) | The HAMA-14 scale measures anxiety symptoms accompanying Major Depressive Disorder (MDD). Each item of the 14-item HAMA was scored from 0 (not present) to 4 (very severe), with a resulting maximum total score of 56. | Baseline and 8 Weeks | 
| Change From Baseline to 8 Week Endpoint in Stroop Color Word Test | This was a psychological test to observe the interference in which disparity between the meaning and color affects reading speed. A subject was given 3 tasks of recognition: reading the printed colored ink (Color Test), reading color words in black ink (Word Test), and interference, reading color words printed in different colored ink (Word-Color Test). The test was scored on the number of correct answers. There were 100 items for each of the three categories and if they made it through the 100 words with time remaining, they would repeat the list. | Baseline and 8 Weeks | 
| Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) | SF-36 assesses quality of life (QoL) on 8 domains and 2 summary scores (mental component summary [MCS] and physical component summary [PCS]). MCS and PCS scores=0-100 (higher scores indicate better QoL). Raw domain scores: general health=5-25; physical functioning=10-30; role-physical=4-20; role-emotional=3-15; social functioning=2-10; bodily pain=2-12; vitality=4-20; mental health=5-25. Using norm based scores, all domains, MCS and PCS scores have average score of 50 with standard deviation of 10. Norm-based score=Z-score*10+50 in each subscale. Range cannot be specified in norm-based scores. | Baseline and 8 Weeks | 
| Number of Participants With Potentially Clinically Significant Changes in Vital Signs During the Study | Vital signs reported are Pulse (beats per minute [bpm]), Systolic Blood Pressure (SBP) (mmHg), and Diastolic Blood Pressure (DBP) (mmHg). | Baseline to 8 Weeks | 
| Significant Changes in Body Weight During the Study | Potentially clinically significant weight loss was defined as any decrease of at least 7 percent (%). Potentially clinically significant weight gain was defined as any increase of at least 7%. | Baseline to 8 Weeks | 
| Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion | The Fridericia correction of the QT interval (QTcF) was used. | Baseline to 8 Weeks | 
| Cytochrome P450 2D6 (CYP2D6) Phenotype Status | CYP2D6 is the primary atomoxetine metabolizing enzyme. Metabolizzer status was determined by focusing on the normal, decreased, and defective allele. Poor metabolizer = defective/defective. Extensive metabolizer is all except for poor metabolizer. | 8 Weeks |