Trial Outcomes & Findings for Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) With Atomoxetine in Young Adults and Its Effects on Functional Outcomes (NCT NCT00510276)

NCT ID: NCT00510276

Last Updated: 2010-04-14

Results Overview

CAARS-Inv:SV is a 30-item scale containing 3 subscales: the Inattention subscale, the Hyperactivity-Impulsivity subscale, and the ADHD Index. The 18-item total ADHD symptom score is the sum of the Inattention and Hyperactivity-Impulsivity subscales. Each item is scored on a 0 to 3 scale (0=not at all, never; 1=just a little, once in a while; 2=pretty much, often; 3=very much, very frequently). The scale assesses symptom severity over the past week. The total score ranges from 0 to 54.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 445 participants
• Primary outcome timeframe: Baseline, Week 12
• Results posted on: 2010-04-14

Participant Flow

The recruitment period was from 16 August 2007 until 19 August 2008 in medical clinics.

Study Period 1 was a screening/washout period. Subjects who did not meet enrollment criteria were excluded from the trial before randomization. 584 participants entered the screening phase, 139 were screen failures. There was an optional 12-week open-label atomoxetine extension phase after the 12-week acute double-blind phase.

Participant milestones

Measure	Atomoxetine 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo twice a day for 12 weeks
Acute Double-Blind Phase STARTED	220	225
Acute Double-Blind Phase COMPLETED	115	130
Acute Double-Blind Phase NOT COMPLETED	105	95
Extension Open-Label Phase STARTED	111	129
Extension Open-Label Phase COMPLETED	78	81
Extension Open-Label Phase NOT COMPLETED	33	48

Reasons for withdrawal

Measure	Atomoxetine 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo twice a day for 12 weeks
Acute Double-Blind Phase Adverse Event	21	6
Acute Double-Blind Phase Entry Criteria Not Met	1	1
Acute Double-Blind Phase Lack of Efficacy	3	4
Acute Double-Blind Phase Lost to Follow-up	48	49
Acute Double-Blind Phase Physician Decision	0	3
Acute Double-Blind Phase Protocol Violation	4	3
Acute Double-Blind Phase Sponsor Decision	2	1
Acute Double-Blind Phase Subject Decision	26	28
Extension Open-Label Phase Adverse Event	9	18
Extension Open-Label Phase Lack of Efficacy	2	7
Extension Open-Label Phase Lost to Follow-up	12	10
Extension Open-Label Phase Physician Decision	2	3
Extension Open-Label Phase Protocol Violation	0	1
Extension Open-Label Phase Sponsor Decision	1	0
Extension Open-Label Phase Subject Decision	7	9

Baseline Characteristics

Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) With Atomoxetine in Young Adults and Its Effects on Functional Outcomes

Baseline characteristics by cohort

Measure	Atomoxetine n=220 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=225 Participants twice a day for 12 weeks	Total n=445 Participants Total of all reporting groups
Age Continuous	24.71 years STANDARD_DEVIATION 3.35 • n=93 Participants	24.68 years STANDARD_DEVIATION 3.48 • n=4 Participants	24.69 years STANDARD_DEVIATION 3.42 • n=27 Participants
Sex: Female, Male Female	92 Participants n=93 Participants	98 Participants n=4 Participants	190 Participants n=27 Participants
Sex: Female, Male Male	128 Participants n=93 Participants	127 Participants n=4 Participants	255 Participants n=27 Participants
Region of Enrollment United States	210 participants n=93 Participants	220 participants n=4 Participants	430 participants n=27 Participants
Region of Enrollment Puerto Rico	10 participants n=93 Participants	5 participants n=4 Participants	15 participants n=27 Participants
Adult Attention-Deficit/Hyperactivity Disorder Quality of Life 29 - Life Outlook Subscale	54.40 units on a scale STANDARD_DEVIATION 15.42 • n=93 Participants	52.49 units on a scale STANDARD_DEVIATION 15.41 • n=4 Participants	53.44 units on a scale STANDARD_DEVIATION 15.43 • n=27 Participants
Adult Attention-Deficit/Hyperactivity Disorder Quality of Life 29 - Psychological Health Subscale	49.89 units on a scale STANDARD_DEVIATION 18.95 • n=93 Participants	50.98 units on a scale STANDARD_DEVIATION 18.20 • n=4 Participants	50.44 units on a scale STANDARD_DEVIATION 18.56 • n=27 Participants
Adult Attention-Deficit/Hyperactivity Disorder Quality of Life 29 - Total Score	45.95 units on a scale STANDARD_DEVIATION 13.74 • n=93 Participants	45.30 units on a scale STANDARD_DEVIATION 13.53 • n=4 Participants	45.62 units on a scale STANDARD_DEVIATION 13.62 • n=27 Participants
Adult Attention-Deficit/Hyperactivity Disorder Quality of Life 29 - relationship subscale	52.76 units on a scale STANDARD_DEVIATION 19.35 • n=93 Participants	52.47 units on a scale STANDARD_DEVIATION 19.67 • n=4 Participants	52.61 units on a scale STANDARD_DEVIATION 19.49 • n=27 Participants
Beck Anxiety Inventory (BAI)	10.98 units on a scale STANDARD_DEVIATION 9.69 • n=93 Participants	9.18 units on a scale STANDARD_DEVIATION 8.47 • n=4 Participants	10.07 units on a scale STANDARD_DEVIATION 9.13 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Behavioral Regulation	62.40 units on a scale STANDARD_DEVIATION 11.91 • n=93 Participants	60.94 units on a scale STANDARD_DEVIATION 10.77 • n=4 Participants	61.66 units on a scale STANDARD_DEVIATION 11.36 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Emotional Control	18.76 units on a scale STANDARD_DEVIATION 5.73 • n=93 Participants	18.22 units on a scale STANDARD_DEVIATION 5.33 • n=4 Participants	18.49 units on a scale STANDARD_DEVIATION 5.53 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - GEC	157.11 units on a scale STANDARD_DEVIATION 22.80 • n=93 Participants	156.12 units on a scale STANDARD_DEVIATION 21.00 • n=4 Participants	156.61 units on a scale STANDARD_DEVIATION 21.89 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Inconsistency	3.22 units on a scale STANDARD_DEVIATION 1.86 • n=93 Participants	3.50 units on a scale STANDARD_DEVIATION 1.97 • n=4 Participants	3.36 units on a scale STANDARD_DEVIATION 1.92 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Infrequency	0.13 units on a scale STANDARD_DEVIATION 0.40 • n=93 Participants	0.15 units on a scale STANDARD_DEVIATION 0.38 • n=4 Participants	0.14 units on a scale STANDARD_DEVIATION 0.39 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Inhibit	18.28 units on a scale STANDARD_DEVIATION 2.77 • n=93 Participants	18.11 units on a scale STANDARD_DEVIATION 2.72 • n=4 Participants	18.19 units on a scale STANDARD_DEVIATION 2.74 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Initiate	18.33 units on a scale STANDARD_DEVIATION 3.11 • n=93 Participants	18.32 units on a scale STANDARD_DEVIATION 3.00 • n=4 Participants	18.33 units on a scale STANDARD_DEVIATION 3.05 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Metacognition Index	94.71 units on a scale STANDARD_DEVIATION 13.69 • n=93 Participants	95.18 units on a scale STANDARD_DEVIATION 12.77 • n=4 Participants	94.95 units on a scale STANDARD_DEVIATION 13.22 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Negativity	2.22 units on a scale STANDARD_DEVIATION 2.16 • n=93 Participants	2.06 units on a scale STANDARD_DEVIATION 2.03 • n=4 Participants	2.14 units on a scale STANDARD_DEVIATION 2.10 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Plan/Organize	23.25 units on a scale STANDARD_DEVIATION 4.02 • n=93 Participants	23.31 units on a scale STANDARD_DEVIATION 3.91 • n=4 Participants	23.28 units on a scale STANDARD_DEVIATION 3.96 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - SHIFT	12.56 units on a scale STANDARD_DEVIATION 2.82 • n=93 Participants	12.36 units on a scale STANDARD_DEVIATION 2.64 • n=4 Participants	12.46 units on a scale STANDARD_DEVIATION 2.73 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Self Monitor	12.80 units on a scale STANDARD_DEVIATION 3.01 • n=93 Participants	12.25 units on a scale STANDARD_DEVIATION 2.89 • n=4 Participants	12.52 units on a scale STANDARD_DEVIATION 2.96 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Task Monitor	14.44 units on a scale STANDARD_DEVIATION 2.36 • n=93 Participants	14.68 units on a scale STANDARD_DEVIATION 2.31 • n=4 Participants	14.56 units on a scale STANDARD_DEVIATION 2.33 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report - Working Memory	19.87 units on a scale STANDARD_DEVIATION 2.73 • n=93 Participants	19.87 units on a scale STANDARD_DEVIATION 2.69 • n=4 Participants	19.87 units on a scale STANDARD_DEVIATION 2.71 • n=27 Participants
Behavior Rating Inventory of Executive Function-Adult Version Self Report- Organization of Materials	18.82 units on a scale STANDARD_DEVIATION 4.07 • n=93 Participants	19.00 units on a scale STANDARD_DEVIATION 3.87 • n=4 Participants	18.91 units on a scale STANDARD_DEVIATION 3.97 • n=27 Participants
Clinical Global Impression-ADHD- Severity (CGI-ADHD-S)	4.79 units on a scale STANDARD_DEVIATION 0.66 • n=93 Participants	4.68 units on a scale STANDARD_DEVIATION 0.64 • n=4 Participants	4.74 units on a scale STANDARD_DEVIATION 0.65 • n=27 Participants
Conners' ADHD Rating Scale Self Report (CAARS-S:SV) Total Score	35.01 units on a scale STANDARD_DEVIATION 8.97 • n=93 Participants	35.69 units on a scale STANDARD_DEVIATION 8.60 • n=4 Participants	35.36 units on a scale STANDARD_DEVIATION 8.78 • n=27 Participants
Conners' Adult ADHD Rating Scale - Investigator Rated:Screening Version Total Score	39.15 units on a scale STANDARD_DEVIATION 7.48 • n=93 Participants	38.95 units on a scale STANDARD_DEVIATION 7.72 • n=4 Participants	39.05 units on a scale STANDARD_DEVIATION 7.59 • n=27 Participants
Driving Behavior Survey Self-Report	79.86 units on a scale STANDARD_DEVIATION 12.89 • n=93 Participants	78.95 units on a scale STANDARD_DEVIATION 12.46 • n=4 Participants	79.41 units on a scale STANDARD_DEVIATION 12.67 • n=27 Participants
Driving Behavior Survey-Other Report	70.90 units on a scale STANDARD_DEVIATION 10.13 • n=93 Participants	78.00 units on a scale STANDARD_DEVIATION 11.24 • n=4 Participants	74.77 units on a scale STANDARD_DEVIATION 11.21 • n=27 Participants
Epworth Sleepiness Scale (ESS)	9.82 units on a scale STANDARD_DEVIATION 4.71 • n=93 Participants	9.60 units on a scale STANDARD_DEVIATION 4.74 • n=4 Participants	9.71 units on a scale STANDARD_DEVIATION 4.72 • n=27 Participants
Fagerstrom Test for Nicotine Dependence (FTND)	2.08 units on a scale STANDARD_DEVIATION 2.10 • n=93 Participants	2.33 units on a scale STANDARD_DEVIATION 2.22 • n=4 Participants	2.20 units on a scale STANDARD_DEVIATION 2.16 • n=27 Participants
Habits Timeline Followback (TLFB) Incidence for Use of Alcohol	0.98 number of alcoholic drinks per day STANDARD_DEVIATION 1.33 • n=93 Participants	1.08 number of alcoholic drinks per day STANDARD_DEVIATION 1.44 • n=4 Participants	1.03 number of alcoholic drinks per day STANDARD_DEVIATION 1.38 • n=27 Participants
Habits Timeline Followback (TLFB) Incidence for Use of Caffeine	1.78 number of caffeinated drinks per day STANDARD_DEVIATION 1.72 • n=93 Participants	1.87 number of caffeinated drinks per day STANDARD_DEVIATION 3.19 • n=4 Participants	1.82 number of caffeinated drinks per day STANDARD_DEVIATION 2.55 • n=27 Participants
Habits Timeline Followback (TLFB) Incidence for Use of Drugs	0.13 ratio STANDARD_DEVIATION 0.15 • n=93 Participants	0.27 ratio STANDARD_DEVIATION 0.37 • n=4 Participants	0.18 ratio STANDARD_DEVIATION 0.24 • n=27 Participants
Habits Timeline Followback (TLFB) Incidence for Use of Marijuana	0.39 number of joints smoked per day STANDARD_DEVIATION 0.59 • n=93 Participants	0.28 number of joints smoked per day STANDARD_DEVIATION 0.38 • n=4 Participants	0.34 number of joints smoked per day STANDARD_DEVIATION 0.50 • n=27 Participants
Habits Timeline Followback (TLFB) Incidence for Use of Nicotine	6.91 number of nicotine-products used per day STANDARD_DEVIATION 7.73 • n=93 Participants	6.41 number of nicotine-products used per day STANDARD_DEVIATION 7.44 • n=4 Participants	6.65 number of nicotine-products used per day STANDARD_DEVIATION 7.57 • n=27 Participants
Montgomery Asberg Depression Rating Scale (MADRS)	6.68 units on a scale STANDARD_DEVIATION 4.28 • n=93 Participants	6.29 units on a scale STANDARD_DEVIATION 4.01 • n=4 Participants	6.48 units on a scale STANDARD_DEVIATION 4.14 • n=27 Participants
Social Adaptation Self-Evaluation Scale (SASS)	36.99 units on a scale STANDARD_DEVIATION 6.17 • n=93 Participants	37.28 units on a scale STANDARD_DEVIATION 5.93 • n=4 Participants	37.14 units on a scale STANDARD_DEVIATION 6.04 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat population was analyzed, including all randomized patients who had both a baseline and at least 1 post baseline score.

CAARS-Inv:SV is a 30-item scale containing 3 subscales: the Inattention subscale, the Hyperactivity-Impulsivity subscale, and the ADHD Index. The 18-item total ADHD symptom score is the sum of the Inattention and Hyperactivity-Impulsivity subscales. Each item is scored on a 0 to 3 scale (0=not at all, never; 1=just a little, once in a while; 2=pretty much, often; 3=very much, very frequently). The scale assesses symptom severity over the past week. The total score ranges from 0 to 54.

Outcome measures

Measure	Atomoxetine n=119 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=134 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change in the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptom Score From Baseline to 12 Week Endpoint	-14.88 units on a scale Standard Error 0.88	-9.82 units on a scale Standard Error 0.85	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Patient-reported outcome measure used to examine the disease-specific functional impariments and quality of life for adults with ADHD. The domains included in the AAQOL are life productivity, psychological health, quality of relationships, and life outlook. Individual items are scored on a five-point Likert-like scale from "not at all/never=1" to "extremely/very often=5". The range of scores is 0 to 100. Consistent with the majority of existing quality of life measures, higher scores on the AAQOL-29 indicate better functioning.

Outcome measures

Measure	Atomoxetine n=117 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=131 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Quality of Life-29 (AAQOL-29) Total Score	15.76 units on a scale Standard Error 1.28	10.95 units on a scale Standard Error 1.23	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Intent-to-treat population was used for analysis. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Patient-reported outcome measure used to examine the disease-specific functional impariments and quality of life for adults with ADHD. This subscale asseses quality of relationships. Individual items are scored on a five-point Likert-like scale from "not at all/never=1" to "extremely/very often=5". The range of scores for this subscale is 0 to 100. Consistent with the majority of existing quality of life measures, higher scores on the AAQOL-29 indicate better functioning.

Outcome measures

Measure	Atomoxetine n=117 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=131 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Quality of Life-29 (AAQOL-29) Relationship Subscale	15.51 units on a scale Standard Error 1.60	9.61 units on a scale Standard Error 1.54	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: An intent-to-treat population was analyzed. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Patient-reported outcome measure used to examine the disease specific functional impairments and quality of life for adults with ADHD. This subscale assesses life productivity. Individual items are scored on a five-point Likert-like scale from "not at all/never=1" to "extremely/very often=5". The range of scores for this subscale is 0 to 100. Consistent with the majority of existing quality of life measures, higher scores on the AAQOL-29 indicate better functioning.

Outcome measures

Measure	Atomoxetine n=117 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=131 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Quality of Life-29 (AAQOL-29) Life Productivity Subscale	20.92 units on a scale Standard Error 1.79	15.18 units on a scale Standard Error 1.72	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: An intent-to-treat population was analyzed. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Patient-reported outcome measure used to examine the disease specific functional impairments and quality of life for adults with ADHD. This subscale asseses the psychological health. Individual items are scored on a five-point Likert-like scale from "not at all/never=1" to "extremely/very often=5". The range of scores for this subscale is 0 to 100. Consistent with the majority of existing quality of life measures, higher scores on the AAQOL-29 indicate better functioning.

Outcome measures

Measure	Atomoxetine n=117 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=131 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Quality of Life-29 (AAQOL-29) Psychological Health Subscale	14.57 units on a scale Standard Error 1.53	10.21 units on a scale Standard Error 1.47	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: An intent-to-treat population was analyzed. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Patient-reported outcome measure used to examine the disease specific functional impairments and quality of life for adults with ADHD. This subscale asseses life outlook. Individual items are scored on a five-point Likert-like scale from "not at all/never=1" to "extremely/very often=5". The range of scores for this subscale is 0 to 100. Consistent with the majority of existing quality of life measures, higher scores on the AAQOL-29 indicate better functioning.

Outcome measures

Measure	Atomoxetine n=117 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=131 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Quality of Life-29 (AAQOL-29) Life Outlook Subscale	9.27 units on a scale Standard Error 1.40	5.87 units on a scale Standard Error 1.33	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Single-item clinician rating of the clinician's assessment of the patient's severity of the ADHD symptoms in relation to the clinician's total experience with ADHD patients. Severity is rated on a 7-point scale (1 = normal, not at all ill; 7 = among the most extremely ill patients). The total score ranges from 1 to 7.

Outcome measures

Measure	Atomoxetine n=192 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=200 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12 Week Endpoint in Clinical Global Impression-ADHD- Severity (CGI-ADHD-S)	-1.10 units on a scale Standard Error 0.08	-0.67 units on a scale Standard Error 0.08	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: An intent-to-treat population was analyzed using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

30-item patient-reported scale with 3 subscales: Inattention subscale, Hyperactivity-Impulsivity subscale, and ADHD Index. 18-item total ADHD symptom score is the sum of the Inattention and Hyperactivity-Impulsivity subscales. Each individual item is scored on a 0 to 3 scale (0 = not at all, never; 1 = just a little, once in a while; 2 = Pretty much, often; 3 = very much, very frequently). The rating scale assesses symptom severity over the past week. The total score ranges from 0 to 54.

Outcome measures

Measure	Atomoxetine n=189 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=197 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12 Week Endpoint in CAARS Self Report (CAARS-S:SV) Total Score	-11.88 units on a scale Standard Error 0.75	-7.84 units on a scale Standard Error 0.73	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

7-point scale modeled after the CGI on which patients rate any change in their overall status that they had experienced since beginning the study drug. The score on this scale ranges from 1 (very much improved) to 7 (very much worse).

Outcome measures

Measure	Atomoxetine n=189 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=197 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Endpoint Scores in Patient Global Impression - Improvement (PGI-I)	3.17 units on a scale Standard Error 0.08	3.42 units on a scale Standard Error 0.08	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Rating scale for severity of depressive mood symptoms, administered by the investigator. The scale consists of 10 items, each rated on a scale from 0 to 6. The MADRS total score is the sum of the 10 items and the score ranges from 0 to 60. Higher scores denote more severe depressive symptoms.

Outcome measures

Measure	Atomoxetine n=173 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=177 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12 Week Endpoint on the Montgomery Asberg Depression Rating Scale (MADRS)	-0.72 units on a scale Standard Error 0.30	-0.30 units on a scale Standard Error 0.30	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward as imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

21-item self-reported screening tool for measuring anxiety severity. Each item is rated on a 4-point Likert scale ranging from 0 (not at all) to 3 (severely; I could barely stand it). Each item is descriptive of subjective, somatic, or panic-related symptoms of anxiety. Patients record how much they have been bothered by each symptom during the past week, including the day the questionnaire is administered. The total score ranges from 0 to 63.

Outcome measures

Measure	Atomoxetine n=151 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=156 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12 Week Endpoint on the Beck Anxiety Inventory (BAI)	-2.58 units on a scale Standard Error 0.66	-2.07 units on a scale Standard Error 0.66	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

AAQOL-29: Patient-reported outcome measure examining disease-specific functional impariments and quality of life for adults with ADHD. The domains included in the AAQOL are life productivity, psychological health, quality of relationships, and life outlook. Consistent with the majority of existing quality of life measures, higher scores on the AAQOL-29 indicate better functioning.

CAARS-Inv:SV: Inattention subscale, Impulsivity subscale, and ADHD Index. Each item is scored on a 0 to 3 scale, assessing symptom severity over the past week. The total score is the sum of all subscale scores.

Outcome measures

Measure	Atomoxetine n=378 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Correlation of Mean Changes From Baseline to 12 Week on the Adult ADHD Quality of Life-29 Total Score and of Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated:Screening Version Total Score	-0.591 correlation coefficient	—	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Variation of the Alcohol Timeline Followback (TLFB) which is a method for assessing the quantity of alcohol consumption on a daily basis. With a calendar as a guide, the interviewee provides a retrospective estimate of daily habits over a specified period of as long as the previous year. The goal is to provide a detailed record of patterns of use that can be used to guide treatment and to assess treatment outcome. Recorded is the number of standard drinks that have been consumed.

Outcome measures

Measure	Atomoxetine n=119 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=121 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12 Week Endpoint on the Habits Timeline Followback (TLFB) Incidence for Use of Alcohol	-0.21 number of alcoholic drinks per day Standard Error 0.09	-0.06 number of alcoholic drinks per day Standard Error 0.09	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Variation of the Alcohol Timeline Followback (TLFB) which is a method for assessing the quantity of alcohol consumption on a daily basis. This subscale assesses the amount of caffeine consumed by an individual. With a calendar as a guide, the interviewee provides a retrospective estimate of daily habits over a specified period of as long as the previous year. The goal is to provide a detailed record of patterns of use that can be used to guide treatment and to assess treatment outcome.

Outcome measures

Measure	Atomoxetine n=162 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=163 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Habits Timeline Followback (TLFB) Incidence for Use of Caffeine	-0.23 number of caffeinated drinks per day Standard Error 0.11	-0.20 number of caffeinated drinks per day Standard Error 0.11	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Variation of the Alcohol Timeline Followback (TLFB) which is a method for assessing the quantity of alcohol consumption on a daily basis. This subscale assesses the amount of recreational drugs other than marijuana an individual consumed and is expressed as the ratio of number of days on which drugs were used over the total number of days, resulting in a total score ranging from 0 to 1. With a calendar as a guide, the interviewee provides a retrospective estimate of daily habits over a specified period of as long as the previous year.

Outcome measures

Measure	Atomoxetine n=2 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=2 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Habits Timeline Followback (TLFB) Incidence for Use of Drugs	0.02 ratio Standard Deviation 0.01	0.02 ratio Standard Deviation 0.23	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Variation of the Alcohol Timeline Followback (TLFB) which is a method for assessing the quantity of alcohol consumption on a daily basis. This subscale assesses the amount of nicotine consumed by an individual. With a calendar as a guide, the interviewee provides a retrospective estimate of daily habits over a specified period of as long as the previous year. The goal is to provide a detailed record of patterns of use that can be used to guide treatment and to assess treatment outcome.

Outcome measures

Measure	Atomoxetine n=70 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=70 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Habits Timeline Followback (TLFB) Incidence for Use of Nicotine	0.01 number of nicotine products per day Standard Error 0.51	-0.81 number of nicotine products per day Standard Error 0.52	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Variation of the Alcohol Timeline Followback (TLFB) which is a method for assessing the quantity of alcohol consumption on a daily basis. With a calendar as a guide, the interviewee provides a retrospective estimate of daily habits over a specified period of as long as the previous year. The goal is to provide a detailed record of patterns of use that can be used to guide treatment and to assess treatment outcome. Recorded is the number of joints that have been consumed.

Outcome measures

Measure	Atomoxetine n=26 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=20 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12 Week Endpoint on the Habits Timeline Followback (TLFB) Incidence for Use of Marijuana	0.09 number of joints per day Standard Error 0.10	0.03 number of joints per day Standard Error 0.12	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The FTND was designed to provide an ordinal measure of nicotine dependence related to cigarette smoking. It contains items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence. The FTND contains 4 yes-no and 2 multiple choice questions and can be used in a self-report format. The items on FTND are scored 0 to 3 for multiple choice items, the items are summed to yield a total score of 0-10 (0=minimum nicotine dependence; 10=maximum nicotine dependence).

Outcome measures

Measure	Atomoxetine n=48 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=42 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12 Week Endpoint on the Fagerstrom Test for Nicotine Dependence (FTND)	0.12 units on a scale Standard Error 0.25	0.43 units on a scale Standard Error 0.27	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was a intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Patient completed scale that consists of 21 items that examine behavior and subjective perception, including satisfaction, self-perception and motivation in participating in and maintaining relationships with family and friends, satisfaction in work, home and leisure activities, and intellectual interests. Each item is scored from 0 to 3, corresponding to minimal and maximal social adjustment, with a total score range from 0 to 60.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=165 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12 Week Endpoint on the Social Adaptation Self-Evaluation Scale (SASS)	1.24 units on a scale Standard Error 0.39	1.46 units on a scale Standard Error 0.39	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward as imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

26 item self-rated driving survey with examples of driving behaviors, e.g.: putting on seat belt, driving within speed limits, yielding the right of way to other drivers. Items are rated on a 4-point scale (1 = not at all or rarely, 2 = sometimes, 3 = often, 4 = very often). The total score is the sum of the 26 items. A driving history is completed by self-report the first time a rater completes the Driving Behavior Survey (Self-Report). The total score ranges from 26 to 104.

Outcome measures

Measure	Atomoxetine n=140 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=142 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Driving Behavior Survey Self-Report	1.93 units on a scale Standard Error 0.98	3.54 units on a scale Standard Error 1.01	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

26-item driving survey completed by someone other than the patient/driver. Examples of driving behaviors included in the survey match those listed in the Self-Report version of the scale. Items are rated on a 4-point scale (1 = not at all or rarely, 2 = sometimes, 3 = often, 4 = very often). The total score is the sum of the 26 items and ranges from 26 to 104.

Outcome measures

Measure	Atomoxetine n=13 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=11 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Driving Behavior Survey-Other Report	3.24 units on a scale Standard Error 3.67	2.63 units on a scale Standard Error 3.96	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A behavioral regulation subscale measures an individuals control over behavior in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Behavior is rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 30 to 90.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Behavioral Regulation Section Score	-8.15 units on a scale Standard Error 0.83	-5.20 units on a scale Standard Error 0.83	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A emotional control subscale assesses an individuals emotional control in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Behavior is rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 10 to 30.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Emotional Control Section Score	-1.98 units on a scale Standard Error 0.36	-1.40 units on a scale Standard Error 0.36	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A GEC rates the global executive composite of the patient in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Behavior is rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 75 to 225.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - GEC Section Score	-22.41 units on a scale Standard Error 1.86	-14.83 units on a scale Standard Error 1.85	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A Inconsistency rates the behavioral inconsistency displayed by the patient in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Behavior is rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 0 to 20.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Inconsistency Section	-0.51 units on a scale Standard Error 0.15	-0.42 units on a scale Standard Error 0.15	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Standardized measure assessing adult executive functioning/self-regulation in his/her everyday environment. Extent to which respondent answers additional items in an unusual and infrequent direction. Form is designed to be completed by adults 18-90 years of age, including adults with wide variety of developmental, systemic, neurological, and psychiatric disorders. Behavior is rated on 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. Total score ranges from 0 to 5.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Infrequency Section	0.27 units on a scale Standard Error 0.05	0.16 units on a scale Standard Error 0.05	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A Inhibit rates an individual's inhibition in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Behavior is rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 8 to 24.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Inhibit Section	-2.62 units on a scale Standard Error 0.23	-1.65 units on a scale Standard Error 0.23	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A Initiate rates an individual's initiative behaviors in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Behavior is rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 8 to 24.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Initiate Section	-2.41 units on a scale Standard Error 0.25	-1.74 units on a scale Standard Error 0.25	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

BRIEF-A Metacognition subscale is a standardized measure assessing individual's ability to systematically solve problems via planning and organization while sustaining these task-completion efforts in active working memory. Form is designed to be completed by adults, including adults with wide variety of developmental, systemic, neurological, and psychiatric disorders. Behavior is rated on a 3-point Likert scale, with 1=behavior never observed, 2=behavior sometimes observed, and 3=behavior often observed - higher ratings indicate greater perceived impairment. Total score ranges from 40 to 120.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Metacognition Section	-14.13 units on a scale Standard Error 1.14	-9.64 units on a scale Standard Error 1.13	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A Negativity asseses an indivduals' perceived negativity in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Behavior is rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 0 to 10.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Negativity Section	-0.85 units on a scale Standard Error 0.14	-0.71 units on a scale Standard Error 0.14	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A Organization of Materials assesses an individuals' organizing skills in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Observations are rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 8 to 24.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Organization of Materials Section	-2.50 units on a scale Standard Error 0.25	-1.85 units on a scale Standard Error 0.25	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A Plan/Organize asseses an individuals' capabilities to plan and organize in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Behavior is rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 10 to 30.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Plan/Organize Section	-3.62 units on a scale Standard Error 0.33	-2.28 units on a scale Standard Error 0.33	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A Shift assess an individuals' shifting between different behaviors in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Observations are rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 6 to 18.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - SHIFT Section	-1.49 units on a scale Standard Error 0.20	-0.96 units on a scale Standard Error 0.20	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A Self Monitor assesses an individuals' capacity to self monitor in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Observations are rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 6 to 18.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Self Monitor Section	-2.03 units on a scale Standard Error 0.20	-1.20 units on a scale Standard Error 0.20	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A Task Monitor assesses an individuals's ability to monitor a task in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Observations are rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 6 to 18.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Task Monitor Section	-2.28 units on a scale Standard Error 0.20	-1.57 units on a scale Standard Error 0.20	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

The BRIEF-A Working Memory assesses an individuals' memory function in his or her everyday environment. The self-report form is designed to be completed by adults 18-90 years of age, including adults with a wide variety of developmental, systemic, neurological, and psychiatric disorders. Observations are rated on a 3-point Likert scale, with 1=behavior is never observed, 2=behavior is sometimes observed, and 3=behavior is often observed - higher ratings indicate greater perceived impairment. The total score ranges from 8 to 24.

Outcome measures

Measure	Atomoxetine n=161 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=167 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Behavior Rating Inventory of Executive Function-Adult Version Self Report (BRIEF-A) - Working Memory Section	-3.48 units on a scale Standard Error 0.26	-2.18 units on a scale Standard Error 0.26	—	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Used to determine the level of daytime sleepiness. The ESS is a self-rated questionnaire with 8 items that describe normative daily situations known to vary in their soporific qualities. Subjects rate the likelihood of dozing off or falling asleep in each of these situations. Each item is rated on a 4-point scale from 0 (would never doze) to 3 (high chance of dozing). The item scores are summed to produce a total score (range of 0-24). Score >10 (95th percentile) are considered to be suggestive of significant daytime sleepiness.

Outcome measures

Measure	Atomoxetine n=187 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=196 Participants twice a day for 12 weeks	Placebo, Smokers	Placebo Non-smokers
Mean Change From Baseline to 12-Week Endpoint on the Epworth Sleepiness Scale (ESS)	-1.76 units on a scale Standard Error 0.29	-1.07 units on a scale Standard Error 0.28	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Baseline smoking status was recorded and associations to response to treatment were determined. Response was defined as 25% or greater decrease in ADHD symptoms as measured by the CAARS-Inv:SV total ADHD symptom score. The 18-item total CAARS-Inv:SV ADHD symptom score is the sum of the Inattention and Hyperactivity-Impulsivity subscales. Each item is scored on a 0 to 3 scale (0=not at all, never; 1=just a little, once in a while; 2=pretty much, often; 3=very much, very frequently). The scale assesses symptom severity over the past week. The total score ranges from 0 to 54.

Outcome measures

Measure	Atomoxetine n=91 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=128 Participants twice a day for 12 weeks	Placebo, Smokers n=94 Participants	Placebo Non-smokers n=131 Participants
Responders by Baseline Smoking Status	54 participants	60 participants	29 participants	53 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Analyzed was an intent-to-treat population using last observation carried forward imputation technique. Included were all randomized patients who had both a baseline and at least 1 post baseline score.

Baseline smoking status was recorded and associations to response to treatment were determined. Strong response was defined as 40% or greater decrease in ADHD symptoms as measured by the CAARS-Inv:SV total ADHD symptom score. The 18-item total CAARS-Inv:SV ADHD symptom score is the sum of the Inattention and Hyperactivity-Impulsivity subscales. Each item is scored on a 0 to 3 scale (0=not at all, never; 1=just a little, once in a while; 2=pretty much, often; 3=very much, very frequently). The scale assesses symptom severity over the past week. The total score ranges from 0 to 54.

Outcome measures

Measure	Atomoxetine n=91 Participants 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=128 Participants twice a day for 12 weeks	Placebo, Smokers n=94 Participants	Placebo Non-smokers n=131 Participants
Strong Responders by Baseline Smoking Status	38 participants	41 participants	19 participants	31 participants

Adverse Events

Atomoxetine

Serious events: 1 serious events

Other events: 147 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 121 other events

Deaths: 0 deaths

Serious adverse events

Measure	Atomoxetine n=220 participants at risk 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=225 participants at risk twice a day for 12 weeks
Gastrointestinal disorders Colitis	0.45% 1/220 • Number of events 1	0.00% 0/225
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/220	0.44% 1/225 • Number of events 1

Other adverse events

Measure	Atomoxetine n=220 participants at risk 20-50 mg twice a day for 12 weeks, then up to an additional 12 weeks	Placebo n=225 participants at risk twice a day for 12 weeks
Gastrointestinal disorders Abdominal discomfort	2.7% 6/220 • Number of events 6	0.89% 2/225 • Number of events 2
Gastrointestinal disorders Constipation	2.7% 6/220 • Number of events 6	0.44% 1/225 • Number of events 1
Gastrointestinal disorders Diarrhoea	1.4% 3/220 • Number of events 3	2.2% 5/225 • Number of events 5
Gastrointestinal disorders Dry mouth	8.6% 19/220 • Number of events 19	2.2% 5/225 • Number of events 5
Gastrointestinal disorders Dyspepsia	5.0% 11/220 • Number of events 12	0.89% 2/225 • Number of events 2
Gastrointestinal disorders Nausea	14.1% 31/220 • Number of events 35	4.9% 11/225 • Number of events 11
Gastrointestinal disorders Vomiting	3.2% 7/220 • Number of events 7	3.1% 7/225 • Number of events 7
General disorders Fatigue	5.9% 13/220 • Number of events 13	5.8% 13/225 • Number of events 14
General disorders Irritability	5.5% 12/220 • Number of events 13	1.8% 4/225 • Number of events 4
Infections and infestations Nasopharyngitis	2.7% 6/220 • Number of events 6	4.4% 10/225 • Number of events 10
Infections and infestations Pharyngitis streptococcal	2.3% 5/220 • Number of events 5	0.44% 1/225 • Number of events 1
Infections and infestations Upper respiratory tract infection	4.5% 10/220 • Number of events 10	5.8% 13/225 • Number of events 13
Investigations Weight decreased	3.2% 7/220 • Number of events 7	0.89% 2/225 • Number of events 2
Metabolism and nutrition disorders Decreased appetite	12.3% 27/220 • Number of events 27	2.2% 5/225 • Number of events 5
Nervous system disorders Dizziness	5.0% 11/220 • Number of events 11	1.3% 3/225 • Number of events 3
Nervous system disorders Headache	5.9% 13/220 • Number of events 15	8.0% 18/225 • Number of events 19
Nervous system disorders Sedation	2.7% 6/220 • Number of events 7	1.3% 3/225 • Number of events 3
Nervous system disorders Somnolence	4.5% 10/220 • Number of events 10	1.8% 4/225 • Number of events 4
Psychiatric disorders Abnormal dreams	2.7% 6/220 • Number of events 6	3.6% 8/225 • Number of events 8
Psychiatric disorders Anxiety	4.1% 9/220 • Number of events 10	2.2% 5/225 • Number of events 5
Psychiatric disorders Insomnia	10.5% 23/220 • Number of events 23	4.4% 10/225 • Number of events 10
Reproductive system and breast disorders Erectile dysfunction	2.3% 5/220 • Number of events 5	0.00% 0/225
Respiratory, thoracic and mediastinal disorders Cough	0.45% 1/220 • Number of events 1	2.2% 5/225 • Number of events 5

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