Atomoxetine Phase 2 Study in Japanese Adult Patients With Attention Deficit/Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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The objective is to assess overall safety and tolerability of atomoxetine in doses up to 120 mg/day in Japanese adult patients who meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for ADHD

Official Title
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An Open-Label Pilot Study for Atomoxetine 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 Impression-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 Hamilton Depression Rating Scale-17 items (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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atomoxetine<br> | Drug: Atomoxetine<br>* 40 mg/day every day (QD), by mouth (PO), for 1 week; 80 mg/day every day, by mouth, for 1 week; 105 mg/day every day, by mouth, for 2 weeks; 120 mg/day every day, by mouth, for 4 weeks<br>* Other names: Strattera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events Leading to Discontinuation |  | over 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Investigator Rated: Screening Version - Japanese Version (CAARS-Inv:SV-J) | Scale=30 items divided between 3 subscales: inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items), using a 4-point scale (0=not at all/never to 3=very much/very frequently). Total ADHD symptom score consisted of 18 items (sum of inattention and hyperactivity-impulsivity subscales) with range of scores from 0 to 54. | baseline and 8 weeks | 
| Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Self Report: Screening Version - Japanese Version (CAARS-S:SV-J) | Scale=30 items divided between 3 subscales: inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items), using a 4-point scale (0=not at all/never to 3=very much/very frequently). Total ADHD symptom score consisted of 18 items (sum of inattention and hyperactivity-impulsivity subscales) with range of scores from 0 to 54. | baseline and 8 weeks | 
| Change From Endpoint to Baseline in Clinical Global Impression-ADHD - Severity | 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 Endpoint to Baseline in Hamilton Depression Rating Scale - 17 Items (HAMD-17) Total Score | 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 Endpoint to Baseline in Hamilton Anxiety Rating Scale - 14 Items (HAMA) Total Score | The 14-item HAMA assesses the severity of anxiety. The investigator talked to the patient about their symptoms over the previous week before the study visit. Each item was scored using a 5-point scale, i.e. 0 = absent to 4 = severe. The total score of HAMA-14 may range from 0 (normal) to 56 (severe). | baseline and 8 weeks | 
| Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores | Derivation of norm-based scoring: Items re-scored to ensure choices were in consistent order and sum up converted score in each subscale; Transform subscale score; Normalize transformed subscale score (i.e. Z-score) using Japanese mean and standard deviation of SF-36v2 subscales. Calculate: norm-based score=Z-score*10+50 in each subscale. | baseline and 8 weeks | 
| Change From Endpoint to Baseline in Stroop Color Word Test | An assessment of response inhibition. Three timed tests: reading color words in black ink; reading the printed colored ink; and reading color words printed in different colored ink. There were 100 items for each of the three test categories and if they made it through the 100 words with time remaining, they would repeat the list. | 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). | over 8 weeks | 
| Number of Participants With Potentially Clinically Significant Changes in Body Weight During the Study | Potentially clinically significant weight loss was defined as any decrease of at least 7%. Potentially clinically significant weight gain was defined as any increase of at least 7%. | over 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. | over 8 weeks | 
| Cytochrome P450 2D6 (CYP2D6) Phenotype Status | CYP2D6 is the primary atomoxetine metabolizing enzyme. Metabolizer 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 |