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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00530335
• Collaborator: (none)
• Enrollment: 45
• Locations: 12
• Arm: 1
• Duration (Months): 7
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: Atomoxetine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Pilot Study for Atomoxetine in Adult Subjects With Attention Deficit/Hyperactivity Disorder
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events Leading to Discontinuation [over 8 weeks]

Secondary Outcome Measures

1. Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Investigator Rated: Screening Version - Japanese Version (CAARS-Inv:SV-J) [baseline and 8 weeks]

   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.

2. Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Self Report: Screening Version - Japanese Version (CAARS-S:SV-J) [baseline and 8 weeks]

   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.

3. Change From Endpoint to Baseline in Clinical Global Impression-ADHD - Severity [baseline and 8 weeks]

   Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).

4. Change From Endpoint to Baseline in Hamilton Depression Rating Scale - 17 Items (HAMD-17) Total Score [baseline and 8 weeks]

   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).

5. Change From Endpoint to Baseline in Hamilton Anxiety Rating Scale - 14 Items (HAMA) Total Score [baseline and 8 weeks]

   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).

6. Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores [baseline and 8 weeks]

   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.

7. Change From Endpoint to Baseline in Stroop Color Word Test [baseline and 8 weeks]

   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.

8. Number of Participants With Potentially Clinically Significant Changes in Vital Signs During the Study [over 8 weeks]

   Vital signs reported are Pulse (beats per minute [bpm]), Systolic Blood Pressure (SBP) (mmHg), and Diastolic Blood Pressure (DBP) (mmHg).

9. Number of Participants With Potentially Clinically Significant Changes in Body Weight During the Study [over 8 weeks]

   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%.

10. Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion [over 8 weeks]

    The Fridericia correction of the QT interval(QTcF) was used.

11. Cytochrome P450 2D6 (CYP2D6) Phenotype Status [8 weeks]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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.	Aichi		Japan	466-8560
2	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
3	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
4	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
5	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
6	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
7	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
8	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
9	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
10	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
11	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
12	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

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00530335
• Other Study ID Numbers: 11821; B4Z-JE-LYED
• First Posted: Sep 17, 2007
• Last Update Posted: Jul 27, 2011
• Last Verified: Jul 1, 2011

• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Period Title: Overall Study
STARTED	45
COMPLETED	39
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Overall Participants	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.12 (8.97)
Sex: Female, Male (Count of Participants)
Female	26 57.8%
Male	19 42.2%
Region of Enrollment (participants) [Number]
Japan	45 100%
Race/Ethnicity (participants) [Number]
Japanese	45 100%
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.0 (0.8)
Conners' Adult ADHD Rating Scale-Inv:SV-J ADHD Index Subscale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	22.3 (5.7)
Conners' Adult ADHD Rating Scale-Inv:SV-J Hyperactive/Impulsive Subscale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	9.8 (6.2)
Conners' Adult ADHD Rating Scale-Inv:SV-J Inattentive Subscale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	21.5 (3.0)
Conners' Adult ADHD Rating Scale-Inv:SV-J Total Symptoms Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	31.2 (7.0)
Conners' Adult ADHD Rating Scale-S:SV-J ADHD Index Subscale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	21.0 (6.8)
Conners' Adult ADHD Rating Scale-S:SV-J Hyperactive/Impulsive Subscale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	10.1 (5.8)
Conners' Adult ADHD Rating Scale-S:SV-J Inattentive Subscale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	19.0 (5.7)
Conners' Adult ADHD Rating Scale-S:SV-J Total Symptoms Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	29.1 (9.7)
Hamilton Anxiety Rating Scale-14 Items Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.2 (5.3)
Hamilton Depression Rating Scale-17 Items Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.2 (3.9)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events Leading to Discontinuation
Time Frame	over 8 weeks

Outcome Measure Data

Analysis Population Description

All three participants who discontinued due to an adverse event were on atomoxetine doses of between 80 mg/day and 105 mg/day.

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
Nausea	1 2.2%
Malaise	1 2.2%
Anorexia	1 2.2%

2. Secondary Outcome

Title	Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Investigator Rated: Screening Version - Japanese Version (CAARS-Inv:SV-J)
Description	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.
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants with Last Observation Carried Forward.

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
Total ADHD Symptoms Score	-15.0 (9.0)
Inattentive Subscale	-9.9 (6.7)
Hyperactivity/Impulsive Subscale	-5.0 (4.6)
ADHD Index Subscale	-9.3 (6.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value comparing difference in Total ADHD Symptoms Score (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value comparing difference in Inattentive Subscale scores (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value comparing difference in Hyperactivity/Impulsive Subscale scores (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value comparing difference in ADHD Index Subscale scores (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Self Report: Screening Version - Japanese Version (CAARS-S:SV-J)
Description	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.
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants with Last Observation Carried Forward.

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
Total ADHD Symptoms Score	-11.9 (10.6)
Inattentive Subscale	-7.0 (7.0)
Hyperactive/Impulsive Subscale	-4.9 (4.8)
ADHD Index Subscale	-6.4 (6.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value comparing difference in Total ADHD Symptoms Score (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value comparing difference in Inattentive Subscale scores (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value comparing difference in Hyperactive/Impulsive Subscale scores (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value comparing difference in ADHD Index Subscale scores (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Change From Endpoint to Baseline in Clinical Global Impression-ADHD - Severity
Description	Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants with Last Observation Carried Forward.

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
Mean (Standard Deviation) [units on a scale]	-1.2 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Change From Endpoint to Baseline in Hamilton Depression Rating Scale - 17 Items (HAMD-17) Total Score
Description	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).
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants with Last Observation Carried Forward.

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
Mean (Standard Deviation) [units on a scale]	0.2 (4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.749
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Change From Endpoint to Baseline in Hamilton Anxiety Rating Scale - 14 Items (HAMA) Total Score
Description	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).
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
Mean (Standard Deviation) [units on a scale]	-0.1 (6.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.886
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores
Description	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.
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants with Last Observation Carried Forward.

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
Physical Component Summary Baseline	47.9 (9.52)
Physical Component Summary Change from Baseline	1.20 (9.64)
Mental Component Summary Baseline	44.46 (7.26)
Mental Component Summary Change from Baseline	0.86 (6.61)
Physical Functioning Baseline	54.74 (5.42)
Physical Functioning Change from Baseline	-0.63 (4.94)
Role-Physical Baseline	44.04 (13.16)
Role-Physical Change from Baseline	2.20 (13.37)
Bodily Pain Baseline	49.55 (11.43)
Bodily Pain Change from Baseline	0.78 (10.28)
General Health Perception Baseline	48.30 (10.12)
General Health Perception Change from Baseline	0.91 (7.21)
Vitality Baseline	43.41 (10.22)
Vitality Change from Baseline	1.23 (8.73)
Social Functioning Baseline	43.21 (14.31)
Social Functioning Change from Baseline	1.17 (13.54)
Role-Emotional Baseline	39.09 (14.16)
Role-Emotional Change from Baseline	2.64 (13.54)
Mental Health Baseline	43.18 (10.45)
Mental Health Change from Baseline	1.80 (7.63)

8. Secondary Outcome

Title	Change From Endpoint to Baseline in Stroop Color Word Test
Description	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.
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants with Last Observation Carried Forward.

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
Word Test Baseline	91.3 (17.9)
Word Test Change from Baseline	4.1 (9.2)
Color Test Baseline	72.8 (14.6)
Color Test Change from Baseline	4.9 (7.8)
Color-Word Test Baseline	51.7 (11.9)
Color-Word Test Change from Baseline	4.2 (8.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	P-value for comparing differences in Word Test number of correct responses (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for comparing differences in Color Test number of correct responses (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	P-value for comparing differences in Color-Word Test number of correct responses (endpoint - baseline).
	Method	t-test, 2 sided
	Comments

9. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Changes in Vital Signs During the Study
Description	Vital signs reported are Pulse (beats per minute [bpm]), Systolic Blood Pressure (SBP) (mmHg), and Diastolic Blood Pressure (DBP) (mmHg).
Time Frame	over 8 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants.

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
High Pulse(bpm)=Increase ≥15 to a value >120	0 0%
Low Pulse(bpm)=Decrease ≥15 to a value <50	0 0%
High SBP(mmHg)=Increase ≥20 to value at least 180	0 0%
Low SBP(mmHg)=Decrease ≥20 to value of at most 90	1 2.2%
High DBP(mmHg)=Increase ≥15 to value at least 105	0 0%
Low DBP(mmHg)=Decrease ≥15 to value of at most 50	0 0%

10. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Changes in Body Weight During the Study
Description	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%.
Time Frame	over 8 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants.

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
Weight Loss=Any Decrease of at Least 7%	4 8.9%
Weight Gain=Any Increase of at Least 7%	0 0%

11. Secondary Outcome

Title	Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion
Description	The Fridericia correction of the QT interval(QTcF) was used.
Time Frame	over 8 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants.

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
QTcF Interval of >450 milliseconds (ms)	1 2.2%
QTcF Interval of >480 milliseconds	0 0%
QTcF Interval of >500 milliseconds	0 0%
QTcF Interval increase from baseline of ≥30 msec	4 8.9%
QTcF Interval increase from baseline of ≥60 msec	0 0%

12. Secondary Outcome

Title	Cytochrome P450 2D6 (CYP2D6) Phenotype Status
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
Measure Participants	45
Extensive Metabolizer	44 97.8%
Poor Metabolizer	1 2.2%

Adverse Events

Arm/Group Title	Atomoxetine
Arm/Group Description	40 mg/day every, by mouth, 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
All Cause Mortality
	Atomoxetine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Atomoxetine
	Affected / at Risk (%)	# Events
Total	0/45 (0%)
Other (Not Including Serious) Adverse Events
	Atomoxetine
	Affected / at Risk (%)	# Events
Total	45/45 (100%)
Cardiac disorders
Palpitations	7/45 (15.6%)	7
Gastrointestinal disorders
Constipation	7/45 (15.6%)	7
Dry mouth	4/45 (8.9%)	4
Dyspepsia	4/45 (8.9%)	5
Nausea	21/45 (46.7%)	24
Stomach discomfort	3/45 (6.7%)	3
General disorders
Malaise	6/45 (13.3%)	6
Pyrexia	3/45 (6.7%)	3
Thirst	9/45 (20%)	9
Infections and infestations
Nasopharyngitis	16/45 (35.6%)	18
Investigations
Electrocardiogram QT prolonged	3/45 (6.7%)	3
Weight decreased	6/45 (13.3%)	6
Metabolism and nutrition disorders
Anorexia	9/45 (20%)	9
Decreased appetite	4/45 (8.9%)	4
Nervous system disorders
Dizziness	4/45 (8.9%)	4
Dysgeusia	3/45 (6.7%)	4
Headache	11/45 (24.4%)	11
Somnolence	9/45 (20%)	10
Tremor	3/45 (6.7%)	3
Psychiatric disorders
Insomnia	3/45 (6.7%)	3
Middle insomnia	4/45 (8.9%)	4
Renal and urinary disorders
Dysuria	4/45 (8.9%)	4
Reproductive system and breast disorders
Dysmenorrhoea	6/45 (13.3%)	9
Vascular disorders
Hot flush	7/45 (15.6%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.