Trial Outcomes & Findings for Atomoxetine Asian Study in Adult Subjects With Attention-Deficit/Hyperactivity Disorder (ADHD) (NCT NCT00636818)

NCT ID: NCT00636818

Last Updated: 2010-11-04

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 45 participants
• Primary outcome timeframe: Baseline to 8 Weeks
• Results posted on: 2010-11-04

Participant Flow

Participant milestones

Measure	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.
Overall Study STARTED	45
Overall Study Received at Least One Dose of Study Drug	44
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	11

Reasons for withdrawal

Measure	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.
Overall Study Adverse Event	1
Overall Study Lost to Follow-up	2
Overall Study Entry Criteria Exclusion	3
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Atomoxetine n=44 Participants 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.
Age Continuous	28.24 years STANDARD_DEVIATION 9.02 • n=93 Participants
Sex: Female, Male Female	14 Participants n=93 Participants
Sex: Female, Male Male	30 Participants n=93 Participants
Region of Enrollment Taiwan	12 participants n=93 Participants
Region of Enrollment China	15 participants n=93 Participants
Region of Enrollment Korea, Republic of	17 participants n=93 Participants
Attention-Deficit/Hyperactivity Disorder (ADHD) Subtype Inattentive	25 participants n=93 Participants
Attention-Deficit/Hyperactivity Disorder (ADHD) Subtype Hyperactive/Impulsive	2 participants n=93 Participants
Attention-Deficit/Hyperactivity Disorder (ADHD) Subtype Mixed	17 participants n=93 Participants
Prior Stimulant Exposure No	30 participants n=93 Participants
Prior Stimulant Exposure Yes	13 participants n=93 Participants
Prior Stimulant Exposure Unknown	1 participants n=93 Participants
Race/Ethnicity East Asian	44 participants n=93 Participants
Height	168.98 centimeters (cm) STANDARD_DEVIATION 6.04 • n=93 Participants
Weight	64.53 kilograms (kg) STANDARD_DEVIATION 9.27 • n=93 Participants

PRIMARY outcome

Timeframe: Baseline to 8 Weeks

Population: Number of participants who received at least one dose of study drug.

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.

Outcome measures

Measure	Atomoxetine n=44 Participants 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.
Discontinuations Due to Adverse Events (AE) Participants with >=1 AE (Discontinuation)	1 participants
Discontinuations Due to Adverse Events (AE) Somnolence (Nervous System Disorder)	1 participants

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: Number of participants who received at least one dose of study drug and had a baseline and at least one post-baseline value. Last observation carried forward.

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.

Outcome measures

Measure	Atomoxetine n=43 Participants 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.
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 Baseline	32.0 units on a scale Standard Deviation 6.3
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 Change from Baseline	-12.8 units on a scale Standard Deviation 10.4

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: Number of participants who received at least one dose of study drug and had a baseline and at least one post-baseline value. 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=43 Participants 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.
Change From Baseline to 8 Week Endpoint in Clinical Global Impressions-ADHD Severity (CGI-ADHD-S) Baseline	4.8 units on a scale Standard Deviation 0.8
Change From Baseline to 8 Week Endpoint in Clinical Global Impressions-ADHD Severity (CGI-ADHD-S) Change from Baseline	-1.7 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: Number of participants who received at least one dose of study drug and had a baseline and at least one post-baseline value. Last observation carried forward.

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.

Outcome measures

Measure	Atomoxetine n=43 Participants 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.
Change From Baseline to 8 Week Endpoint in Conners' Adult ADHD Rating Scale-Self Rated:Screening Version (CAARS-S:SV) Total ADHD Symptom Score Baseline	30.6 units on a scale Standard Deviation 9.7
Change From Baseline to 8 Week Endpoint in Conners' Adult ADHD Rating Scale-Self Rated:Screening Version (CAARS-S:SV) Total ADHD Symptom Score Change from Baseline	-12.1 units on a scale Standard Deviation 10.2

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: Number of participants who received at least one dose of study drug and had a baseline and at least one post-baseline value. 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=42 Participants 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.
Change From Baseline to 8 Week Endpoint in 17-Item Hamilton Depression Rating Scale (HAMD-17) Baseline	4.8 units on a scale Standard Deviation 3.9
Change From Baseline to 8 Week Endpoint in 17-Item Hamilton Depression Rating Scale (HAMD-17) Change from Baseline	-1.5 units on a scale Standard Deviation 3.8

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: Number of participants who received at least one dose of study drug and had a baseline and at least one post-baseline value. Last observation carried forward.

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.

Outcome measures

Measure	Atomoxetine n=42 Participants 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.
Change From Baseline to 8 Week Endpoint in Hamilton Anxiety Rating Scale (HAMA-14) Baseline	6.7 units on a scale Standard Deviation 4.7
Change From Baseline to 8 Week Endpoint in Hamilton Anxiety Rating Scale (HAMA-14) Change from Baseline	-2.0 units on a scale Standard Deviation 4.4

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: Number of participants who received at least one dose of study drug and had a baseline and at least one post-baseline value. Last observation carried forward.

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.

Outcome measures

Measure	Atomoxetine n=42 Participants 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.
Change From Baseline to 8 Week Endpoint in Stroop Color Word Test Word Test: Baseline	82.4 number of correct answers Standard Deviation 16.6
Change From Baseline to 8 Week Endpoint in Stroop Color Word Test Word Test: Change from Baseline	4.5 number of correct answers Standard Deviation 9.9
Change From Baseline to 8 Week Endpoint in Stroop Color Word Test Color Test: Baseline	68.7 number of correct answers Standard Deviation 14.8
Change From Baseline to 8 Week Endpoint in Stroop Color Word Test Color Test: Change from Baseline	4.8 number of correct answers Standard Deviation 10.6
Change From Baseline to 8 Week Endpoint in Stroop Color Word Test Color-Word Test: Baseline	49.0 number of correct answers Standard Deviation 16.5
Change From Baseline to 8 Week Endpoint in Stroop Color Word Test Color-Word Test: Change from Baseline	3.5 number of correct answers Standard Deviation 15.4

SECONDARY outcome

Timeframe: Baseline and 8 Weeks

Population: Number of participants who received at least one dose of study drug and had a baseline and at least one post-baseline value. Last observation carried forward.

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.

Outcome measures

Measure	Atomoxetine n=42 Participants 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.
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Physical Component Summary: Baseline	46.77 T-Score Standard Deviation 9.11
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Physical Component Summary: Change from Baseline	-0.38 T-Score Standard Deviation 9.23
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Mental Component Summary: Baseline	43.71 T-Score Standard Deviation 6.93
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Mental Component Summary: Change from Baseline	3.62 T-Score Standard Deviation 5.36
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Physical Functioning: Baseline	53.12 T-Score Standard Deviation 6.79
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Physical Functioning: Change from Baseline	-3.02 T-Score Standard Deviation 9.09
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Role-Physical: Baseline	43.58 T-Score Standard Deviation 11.36
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Role-Physical: Change from Baseline	1.30 T-Score Standard Deviation 10.94
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Bodily Pain: Baseline	50.46 T-Score Standard Deviation 10.71
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Bodily Pain: Change from Baseline	1.32 T-Score Standard Deviation 9.31
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) General Health Perception: Baseline	47.81 T-Score Standard Deviation 9.67
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) General Health Perception: Change from Baseline	2.48 T-Score Standard Deviation 9.17
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Vitality: Baseline	43.73 T-Score Standard Deviation 8.63
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Vitality: Change from Baseline	2.78 T-Score Standard Deviation 8.61
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Social Functioning: Baseline	40.97 T-Score Standard Deviation 11.36
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Social Functioning: Change from Baseline	2.82 T-Score Standard Deviation 10.39
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Role-Emotional: Baseline	36.63 T-Score Standard Deviation 11.59
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Role-Emotional: Change from Baseline	5.46 T-Score Standard Deviation 13.05
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Mental Health: Baseline	40.38 T-Score Standard Deviation 9.42
Change From Baseline to 8 Week Endpoint in Short Form-36 Version 2 (SF-36v2) Mental Health: Change from Baseline	5.51 T-Score Standard Deviation 8.04

SECONDARY outcome

Timeframe: Baseline to 8 Weeks

Population: Number of participants with baseline and post-baseline values.

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=44 Participants 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.
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 SBP (mmHg)=Increase ≥20 to a value >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 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: Baseline to 8 Weeks

Population: Number of participants with baseline and post-baseline values.

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%.

Outcome measures

Measure	Atomoxetine n=44 Participants 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.
Significant Changes in Body Weight During the Study Weight Loss = Any Decrease of at Least 7%	5 participants
Significant Changes in Body Weight During the Study Weight Gain = Any Increase of at Least 7%	0 participants

SECONDARY outcome

Timeframe: Baseline to 8 Weeks

Population: Number of participants with baseline and post-baseline values.

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

Outcome measures

Measure	Atomoxetine n=42 Participants 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.
Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion QTcF Interval of >450 milliseconds (msec)	0 participants
Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion QTcF Interval of >480 msec	0 participants
Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion QTcF Interval of >500 msec	0 participants
Number of Participants With Abnormal QTc Interval Based on International Conference on Harmonisation Criterion QTcF Interval Increase from Baseline of ≥30 msec	1 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

Population: Number of participants who received at least one dose of study drug.

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.

Outcome measures

Measure	Atomoxetine n=44 Participants 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.
Cytochrome P450 2D6 (CYP2D6) Phenotype Status Extensive Metabolizer	44 participants
Cytochrome P450 2D6 (CYP2D6) Phenotype Status Poor Metabolizer	0 participants

Adverse Events

Atomoxetine

Serious events: 1 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Measure

Atomoxetine n=44 participants at risk 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.

Infections and infestations Hand-foot-and-mouth disease

2.3% 1/44 • Number of events 1

Other adverse events

Measure	Atomoxetine n=44 participants at risk 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.
Cardiac disorders Palpitations	11.4% 5/44 • Number of events 6
Gastrointestinal disorders Dry mouth	11.4% 5/44 • Number of events 5
Gastrointestinal disorders Nausea	36.4% 16/44 • Number of events 19
Gastrointestinal disorders Vomiting	9.1% 4/44 • Number of events 5
General disorders Asthenia	9.1% 4/44 • Number of events 4
General disorders Fatigue	13.6% 6/44 • Number of events 6
General disorders Irritability	6.8% 3/44 • Number of events 3
Metabolism and nutrition disorders Anorexia	6.8% 3/44 • Number of events 3
Metabolism and nutrition disorders Decreased appetite	15.9% 7/44 • Number of events 8
Nervous system disorders Dizziness	34.1% 15/44 • Number of events 19
Nervous system disorders Headache	11.4% 5/44 • Number of events 5
Nervous system disorders Somnolence	29.5% 13/44 • Number of events 13
Psychiatric disorders Insomnia	15.9% 7/44 • Number of events 7
Skin and subcutaneous tissue disorders Hyperhidrosis	6.8% 3/44 • Number of events 3

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