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

An Open-Label Pilot Study for Atomoxetine in Adult Subjects With Attention Deficit/Hyperactivity Disorder

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

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: Atomoxetine

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 466-8560
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Chiba, Japan, 272-8516
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Fukushima, Japan, 960-1295
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Hokkaido, Japan, 060-8648
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Hyogo, Japan, 661-0002
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Ishikawa, Japan, 920-8641
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Kanagawa, Japan, 259-1193
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Kumamoto, Japan, 862-0920
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Kyoto, Japan, 606-8507
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Nara, Japan, 634-8522
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Saitama, Japan, 350-0495
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Tokyo, Japan, 160-0023
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atomoxetine	Drug: Atomoxetine; 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; Other Names: LY139603; Strattera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Takahashi M, Takita Y, Goto T, Ichikawa H, Saito K, Matsumoto H, Tanaka Y. An open-label, dose-titration tolerability study of atomoxetine hydrochloride in Japanese adults with attention-deficit/hyperactivity disorder. Psychiatry Clin Neurosci. 2011 Feb;65(1):55-63. doi: 10.1111/j.1440-1819.2010.02159.x.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: September 14, 2007
• First Submitted That Met QC Criteria: September 14, 2007
• First Posted (Estimate): September 17, 2007

Study Record Updates

• Last Update Posted (Estimate): July 27, 2011
• Last Update Submitted That Met QC Criteria: July 25, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride
• Other Study ID Numbers: 11821; B4Z-JE-LYED (Other Identifier: Eli Lilly and Company)