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

An Open Study of Atomoxetine (LY139603) in Adult Subjects With Attention-deficit/Hyperactivity Disorder

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).

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

• China
  • Beijing, China, 100088
    • 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.
  • Changsha, China, 410011
    • 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.
  • Guang Zhou, China, 560370
    • 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.
• Korea, Republic of
  • Busan, Korea, Republic of, 602739
    • 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.
  • In Cheon, Korea, Republic of, 405-760
    • 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.
  • Jeon Ju-City, Korea, Republic of, 561-712
    • 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.
  • Seoul, Korea, Republic of, 120-752
    • 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.
• Taiwan
  • Neihu Taipei, Taiwan, 114
    • 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.
  • Niao Sung Hsiang, Taiwan, 833
    • 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.
  • Taipei, Taiwan, 100
    • 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.
  • Tao-Yuan, Taiwan, 333
    • 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:

1. at least 18 years of age
2. 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
3. have a Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) score of 4 (moderate symptoms) or greater

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Patients who have been diagnosed (DSM-IV) with a pervasive developmental disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Atomoxetine

Drug: Atomoxetine; 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.; Other Names: LY139603; Strattera

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) Mon - Fri 9 AM - 5PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: March 7, 2008
• First Submitted That Met QC Criteria: March 7, 2008
• First Posted (Estimate): March 14, 2008

Study Record Updates

• Last Update Posted (Estimate): November 4, 2010
• Last Update Submitted That Met QC Criteria: October 20, 2010
• Last Verified: October 1, 2010

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: 12112 (Research Ethic committee of Maisonneuve Rosemont Hospital); B4Z-JE-LYEH (Other Identifier: Eli Lilly and Company)