Trial Outcomes & Findings for Atomoxetine Phase 2 Study in Japanese Adult Patients With Attention Deficit/Hyperactivity Disorder (ADHD) (NCT NCT00530335)

NCT ID: NCT00530335

Last Updated: 2011-07-27

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 45 participants
• Primary outcome timeframe: over 8 weeks
• Results posted on: 2011-07-27

Participant Flow

Participant milestones

Measure	Atomoxetine 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 Study STARTED	45
Overall Study COMPLETED	39
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	Atomoxetine 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 Study Adverse Event	3
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	1
Overall Study Physician Decision	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Atomoxetine n=45 Participants 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
Age Continuous	33.12 years STANDARD_DEVIATION 8.97 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Region of Enrollment Japan	45 participants n=5 Participants
Race/Ethnicity Japanese	45 participants n=5 Participants
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale	5.0 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants
Conners' Adult ADHD Rating Scale-Inv:SV-J ADHD Index Subscale	22.3 units on a scale STANDARD_DEVIATION 5.7 • n=5 Participants
Conners' Adult ADHD Rating Scale-Inv:SV-J Hyperactive/Impulsive Subscale	9.8 units on a scale STANDARD_DEVIATION 6.2 • n=5 Participants
Conners' Adult ADHD Rating Scale-Inv:SV-J Inattentive Subscale	21.5 units on a scale STANDARD_DEVIATION 3.0 • n=5 Participants
Conners' Adult ADHD Rating Scale-Inv:SV-J Total Symptoms Score	31.2 units on a scale STANDARD_DEVIATION 7.0 • n=5 Participants
Conners' Adult ADHD Rating Scale-S:SV-J ADHD Index Subscale	21.0 units on a scale STANDARD_DEVIATION 6.8 • n=5 Participants
Conners' Adult ADHD Rating Scale-S:SV-J Hyperactive/Impulsive Subscale	10.1 units on a scale STANDARD_DEVIATION 5.8 • n=5 Participants
Conners' Adult ADHD Rating Scale-S:SV-J Inattentive Subscale	19.0 units on a scale STANDARD_DEVIATION 5.7 • n=5 Participants
Conners' Adult ADHD Rating Scale-S:SV-J Total Symptoms Score	29.1 units on a scale STANDARD_DEVIATION 9.7 • n=5 Participants
Hamilton Anxiety Rating Scale-14 Items Total Score	6.2 units on a scale STANDARD_DEVIATION 5.3 • n=5 Participants
Hamilton Depression Rating Scale-17 Items Total Score	4.2 units on a scale STANDARD_DEVIATION 3.9 • n=5 Participants

PRIMARY outcome

Timeframe: over 8 weeks

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

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Number of Participants With Adverse Events Leading to Discontinuation Nausea	1 participants
Number of Participants With Adverse Events Leading to Discontinuation Malaise	1 participants
Number of Participants With Adverse Events Leading to Discontinuation Anorexia	1 participants

SECONDARY outcome

Timeframe: baseline and 8 weeks

Population: All enrolled participants with Last Observation Carried Forward.

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.

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Investigator Rated: Screening Version - Japanese Version (CAARS-Inv:SV-J) Total ADHD Symptoms Score	-15.0 units on a scale Standard Deviation 9.0
Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Investigator Rated: Screening Version - Japanese Version (CAARS-Inv:SV-J) Inattentive Subscale	-9.9 units on a scale Standard Deviation 6.7
Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Investigator Rated: Screening Version - Japanese Version (CAARS-Inv:SV-J) Hyperactivity/Impulsive Subscale	-5.0 units on a scale Standard Deviation 4.6
Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Investigator Rated: Screening Version - Japanese Version (CAARS-Inv:SV-J) ADHD Index Subscale	-9.3 units on a scale Standard Deviation 6.4

SECONDARY outcome

Timeframe: baseline and 8 weeks

Population: All enrolled participants with Last Observation Carried Forward.

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.

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Self Report: Screening Version - Japanese Version (CAARS-S:SV-J) ADHD Index Subscale	-6.4 units on a scale Standard Deviation 6.8
Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Self Report: Screening Version - Japanese Version (CAARS-S:SV-J) Total ADHD Symptoms Score	-11.9 units on a scale Standard Deviation 10.6
Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Self Report: Screening Version - Japanese Version (CAARS-S:SV-J) Inattentive Subscale	-7.0 units on a scale Standard Deviation 7.0
Change From Endpoint to Baseline in Connors's Adult ADHD Rating Scale-Self Report: Screening Version - Japanese Version (CAARS-S:SV-J) Hyperactive/Impulsive Subscale	-4.9 units on a scale Standard Deviation 4.8

SECONDARY outcome

Timeframe: baseline and 8 weeks

Population: All enrolled participants with Last Observation Carried Forward.

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

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Change From Endpoint to Baseline in Clinical Global Impression-ADHD - Severity	-1.2 units on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: baseline and 8 weeks

Population: All enrolled participants with Last Observation Carried Forward.

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).

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Change From Endpoint to Baseline in Hamilton Depression Rating Scale - 17 Items (HAMD-17) Total Score	0.2 units on a scale Standard Deviation 4.2

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Change From Endpoint to Baseline in Hamilton Anxiety Rating Scale - 14 Items (HAMA) Total Score	-0.1 units on a scale Standard Deviation 6.2

SECONDARY outcome

Timeframe: baseline and 8 weeks

Population: All enrolled participants with Last Observation Carried Forward.

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.

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Mental Component Summary Change from Baseline	0.86 units on a scale Standard Deviation 6.61
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Mental Health Baseline	43.18 units on a scale Standard Deviation 10.45
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Mental Health Change from Baseline	1.80 units on a scale Standard Deviation 7.63
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Physical Component Summary Baseline	47.9 units on a scale Standard Deviation 9.52
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Physical Component Summary Change from Baseline	1.20 units on a scale Standard Deviation 9.64
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Mental Component Summary Baseline	44.46 units on a scale Standard Deviation 7.26
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Physical Functioning Baseline	54.74 units on a scale Standard Deviation 5.42
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Physical Functioning Change from Baseline	-0.63 units on a scale Standard Deviation 4.94
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Role-Physical Baseline	44.04 units on a scale Standard Deviation 13.16
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Role-Physical Change from Baseline	2.20 units on a scale Standard Deviation 13.37
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Bodily Pain Baseline	49.55 units on a scale Standard Deviation 11.43
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Bodily Pain Change from Baseline	0.78 units on a scale Standard Deviation 10.28
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores General Health Perception Baseline	48.30 units on a scale Standard Deviation 10.12
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores General Health Perception Change from Baseline	0.91 units on a scale Standard Deviation 7.21
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Vitality Baseline	43.41 units on a scale Standard Deviation 10.22
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Vitality Change from Baseline	1.23 units on a scale Standard Deviation 8.73
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Social Functioning Baseline	43.21 units on a scale Standard Deviation 14.31
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Social Functioning Change from Baseline	1.17 units on a scale Standard Deviation 13.54
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Role-Emotional Baseline	39.09 units on a scale Standard Deviation 14.16
Change From Endpoint to Baseline in 36-item Short-Form Health Survey (SF-36v2) Norm-based Subdomain and Summary Scores Role-Emotional Change from Baseline	2.64 units on a scale Standard Deviation 13.54

SECONDARY outcome

Timeframe: baseline and 8 weeks

Population: All enrolled participants with Last Observation Carried Forward.

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.

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Change From Endpoint to Baseline in Stroop Color Word Test Word Test Baseline	91.3 number of correct answers Standard Deviation 17.9
Change From Endpoint to Baseline in Stroop Color Word Test Word Test Change from Baseline	4.1 number of correct answers Standard Deviation 9.2
Change From Endpoint to Baseline in Stroop Color Word Test Color Test Baseline	72.8 number of correct answers Standard Deviation 14.6
Change From Endpoint to Baseline in Stroop Color Word Test Color Test Change from Baseline	4.9 number of correct answers Standard Deviation 7.8
Change From Endpoint to Baseline in Stroop Color Word Test Color-Word Test Baseline	51.7 number of correct answers Standard Deviation 11.9
Change From Endpoint to Baseline in Stroop Color Word Test Color-Word Test Change from Baseline	4.2 number of correct answers Standard Deviation 8.8

SECONDARY outcome

Timeframe: over 8 weeks

Population: All enrolled participants.

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

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Number of Participants With Potentially Clinically Significant Changes in Vital Signs During the Study High SBP(mmHg)=Increase ≥20 to value at least 180	0 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs During the Study Low SBP(mmHg)=Decrease ≥20 to value of at most 90	1 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs During the Study High Pulse(bpm)=Increase ≥15 to a value >120	0 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs During the Study Low Pulse(bpm)=Decrease ≥15 to a value <50	0 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs During the Study High DBP(mmHg)=Increase ≥15 to value at least 105	0 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs During the Study Low DBP(mmHg)=Decrease ≥15 to value of at most 50	0 participants

SECONDARY outcome

Timeframe: over 8 weeks

Population: All enrolled participants.

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%.

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Number of Participants With Potentially Clinically Significant Changes in Body Weight During the Study Weight Loss=Any Decrease of at Least 7%	4 participants
Number of Participants With Potentially Clinically Significant Changes in Body Weight During the Study Weight Gain=Any Increase of at Least 7%	0 participants

SECONDARY outcome

Timeframe: over 8 weeks

Population: All enrolled participants.

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

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion QTcF Interval of >450 milliseconds (ms)	1 participants
Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion QTcF Interval of >480 milliseconds	0 participants
Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion QTcF Interval of >500 milliseconds	0 participants
Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion QTcF Interval increase from baseline of ≥30 msec	4 participants
Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion QTcF Interval increase from baseline of ≥60 msec	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Atomoxetine n=45 Participants 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
Cytochrome P450 2D6 (CYP2D6) Phenotype Status Extensive Metabolizer	44 participants
Cytochrome P450 2D6 (CYP2D6) Phenotype Status Poor Metabolizer	1 participants

Adverse Events

Atomoxetine

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Atomoxetine n=45 participants at risk 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
Cardiac disorders Palpitations	15.6% 7/45 • Number of events 7
Gastrointestinal disorders Constipation	15.6% 7/45 • Number of events 7
Gastrointestinal disorders Dry mouth	8.9% 4/45 • Number of events 4
Gastrointestinal disorders Dyspepsia	8.9% 4/45 • Number of events 5
Gastrointestinal disorders Nausea	46.7% 21/45 • Number of events 24
Gastrointestinal disorders Stomach discomfort	6.7% 3/45 • Number of events 3
General disorders Malaise	13.3% 6/45 • Number of events 6
General disorders Pyrexia	6.7% 3/45 • Number of events 3
General disorders Thirst	20.0% 9/45 • Number of events 9
Infections and infestations Nasopharyngitis	35.6% 16/45 • Number of events 18
Investigations Electrocardiogram QT prolonged	6.7% 3/45 • Number of events 3
Investigations Weight decreased	13.3% 6/45 • Number of events 6
Metabolism and nutrition disorders Anorexia	20.0% 9/45 • Number of events 9
Metabolism and nutrition disorders Decreased appetite	8.9% 4/45 • Number of events 4
Nervous system disorders Dizziness	8.9% 4/45 • Number of events 4
Nervous system disorders Dysgeusia	6.7% 3/45 • Number of events 4
Nervous system disorders Headache	24.4% 11/45 • Number of events 11
Nervous system disorders Somnolence	20.0% 9/45 • Number of events 10
Nervous system disorders Tremor	6.7% 3/45 • Number of events 3
Psychiatric disorders Insomnia	6.7% 3/45 • Number of events 3
Psychiatric disorders Middle insomnia	8.9% 4/45 • Number of events 4
Renal and urinary disorders Dysuria	8.9% 4/45 • Number of events 4
Reproductive system and breast disorders Dysmenorrhoea	13.3% 6/45 • Number of events 9
Vascular disorders Hot flush	15.6% 7/45 • Number of events 7

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60