Trial Outcomes & Findings for A Long Term Follow-Up Study for Asian Adult Patients With Attention Deficit Hyperactivity Disorder (NCT NCT00969618)

NCT ID: NCT00969618

Last Updated: 2012-12-12

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 211 participants
• Primary outcome timeframe: Baseline through 48 weeks
• Results posted on: 2012-12-12

Participant Flow

Participant milestones

Measure	Atomoxetine 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Overall Study STARTED	211
Overall Study COMPLETED	133
Overall Study NOT COMPLETED	78

Reasons for withdrawal

Measure	Atomoxetine 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Overall Study Adverse Event	29
Overall Study Entry Criteria Not Met	3
Overall Study Lack of Efficacy	2
Overall Study Lost to Follow-up	7
Overall Study Physician Decision	1
Overall Study Protocol Violation	9
Overall Study Withdrawal by Subject	27

Baseline Characteristics

A Long Term Follow-Up Study for Asian Adult Patients With Attention Deficit Hyperactivity Disorder

Baseline characteristics by cohort

Measure	Atomoxetine n=211 Participants 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Age Continuous	32.6 years STANDARD_DEVIATION 7.5 • n=93 Participants
Sex: Female, Male Female	105 Participants n=93 Participants
Sex: Female, Male Male	106 Participants n=93 Participants
Race/Ethnicity, Customized Asian	211 participants n=93 Participants
Region of Enrollment Japan	211 participants n=93 Participants

PRIMARY outcome

Timeframe: Baseline through 48 weeks

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

Outcome measures

Measure	Atomoxetine n=211 Participants 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Number of Participants With Adverse Events Leading to Discontinuation	29 participant Interval 9.1 to 18.4

SECONDARY outcome

Timeframe: Baseline, 48 weeks

Population: All participants who received at least one dose of study drug, and had a baseline and at least one post-baseline CAARS measurement. Last observation carried forward (LOCF) principle was used.

CAARS-Inv:SV-J is a 30-item scale containing 3 subscales: inattention (9 items), hyperactivity/impulsivity (9 items), and attention deficit hyperactivity disorder (ADHD) Index (12 items). Each item is scored 0-3 (0=not at all/never; 1=just a little/once in a while; 2=pretty much/often; 3=very much/very frequently). Total ADHD symptoms score=sum of the inattention subscales (scores range from 0-27) and hyperactivity/impulsivity subscales (scores range from 0-27) with a total score range of 0-54. The ADHD Index scores range from 0-36. Higher scores indicate greater impairment.

Outcome measures

Measure	Atomoxetine n=211 Participants 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Mean Change From Baseline to 48 Weeks Endpoint in the Conners' Adult Attention-Deficit Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version-Japanese (CAARS-Inv:SV-J) Total ADHD Symptoms Score	-7.3 units on a scale Standard Deviation 8.1
Mean Change From Baseline to 48 Weeks Endpoint in the Conners' Adult Attention-Deficit Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version-Japanese (CAARS-Inv:SV-J) Inattention Subscale Score	-4.6 units on a scale Standard Deviation 5.1
Mean Change From Baseline to 48 Weeks Endpoint in the Conners' Adult Attention-Deficit Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version-Japanese (CAARS-Inv:SV-J) Hyperactivity/Impulsivity Subscale Score	-2.7 units on a scale Standard Deviation 4.2
Mean Change From Baseline to 48 Weeks Endpoint in the Conners' Adult Attention-Deficit Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version-Japanese (CAARS-Inv:SV-J) ADHD Index Subscale Score	-5.0 units on a scale Standard Deviation 5.9

SECONDARY outcome

Timeframe: Baseline, 48 weeks

Population: All participants who received at least one dose of study drug, and had a baseline and at least one post-baseline AAQoL measurement. Last observation carried forward (LOCF) principle was used.

AAQoL is a 29 items participant completed questionnaire rated on a 5-point Likert scale from 1 (Not at all/ Never) to 5 (Extremely/Very Often). AAQoL total (all 29 items) and 4 subscale scores: Life Productivity (11 items); Psychological Health (6 items); Life Outlook (7 items); Relationships (5 items). Total score is computed by (1) reversing scores for all items except the 7 items in the Life Outlook subscale; (2) transforming scores to 0-100 scale (1=0; 2=25; 3=50; 4=75; 5=100); (3) summing item scores and dividing by the item count. Higher total scores indicate better quality of life.

Outcome measures

Measure	Atomoxetine n=206 Participants 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Mean Change From Baseline to 48 Weeks Endpoint in the Adult Attention-Deficit/Hyperactivity Disorder Quality of Life (AAQoL)-29 Scores	4.46 units on a scale Standard Deviation 13.44

SECONDARY outcome

Timeframe: Baseline, 48 weeks

Population: All participants who received at least one dose of study drug, and had a baseline and at least one post-baseline BRIEF-A self report measurement. Last observation carried forward (LOCF) principle was used.

A 75-item standardized self-reported measure comprised of 3 subscales. Each item is rated on a 3-point Likert scale: 1 (behavior never observed) to 3 (behavior often observed). Global executive composite (GEC) subscale rates participant's GEC in everyday environment (75- 225 total score). Behavioral regulation subscale measures participant's control over behavior (30-90 total score). Metacognition subscale assesses systematic problem-solving ability while sustaining these task-completion efforts in active working memory (40-120 total score). Higher subscale ratings indicate greater perceived impairment.

Outcome measures

Measure	Atomoxetine n=206 Participants 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Mean Change From Baseline to 48 Weeks Endpoint in the Behavior Rating Inventory of Executive Function -Adult (BRIEF-A) Version: Self Report (BRIEF-A:Self Report ) GEC Subscale Score	-10.4 units on a scale Standard Deviation 21.3
Mean Change From Baseline to 48 Weeks Endpoint in the Behavior Rating Inventory of Executive Function -Adult (BRIEF-A) Version: Self Report (BRIEF-A:Self Report ) Behavioral Regulation Subscale Score	-3.6 units on a scale Standard Deviation 9.2
Mean Change From Baseline to 48 Weeks Endpoint in the Behavior Rating Inventory of Executive Function -Adult (BRIEF-A) Version: Self Report (BRIEF-A:Self Report ) Metacognition Subscale Score	-6.8 units on a scale Standard Deviation 13.6

SECONDARY outcome

Timeframe: Baseline, 48 weeks

Population: All participants who received at least one dose of study drug, and had a baseline and at least one post-baseline HAMA-14 measurement. Last observation carried forward (LOCF) principle was used.

The HAMA-14 instrument consists of 14 items that provide an overall measure of general anxiety, including psychic anxiety and somatic anxiety. This instrument is completed by the clinician based on his or her assessment of the participant. Each item is rated on a 5-point scale of 0 (absent) to 4 (very severe). Total score is the sum of the 14 items and ranges from 0 (normal) to 56 (severe). Higher scores indicate greater anxiety.

Outcome measures

Measure	Atomoxetine n=198 Participants 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Mean Change From Baseline to 48 Weeks Endpoint in Comorbid, Anxiety Symptoms, as Measured by Hamilton Anxiety Rating Scale-14 (HAMA-14) Items	0.3 units on a scale Standard Deviation 3.1

SECONDARY outcome

Timeframe: Baseline, 48 weeks

Population: All participants who received at least one dose of study drug, and had a baseline and at least one post-baseline CGI-ADHD-S measurement. Last observation carried forward (LOCF) principle was used.

The CGI-ADHD-S is a single-item rating of the clinician's assessment of the overall severity of the participant's ADHD symptoms in relation to the clinician's total experience with ADHD participants. CGI-ADHD-S measures severity of the participant's overall severity of ADHD symptoms: 1 (normal, not at all ill) to 7 (among the most extremely ill participants).

Outcome measures

Measure	Atomoxetine n=211 Participants 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Mean Change From Baseline to 48 Weeks Endpoint in Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder-Severity (CGI-ADHD-S)	-0.8 units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline, 48 weeks

Population: All participants who received at least one dose of study drug, and had a baseline and at least one post-baseline BRIEF-A Informant scores measurement. Last observation carried forward (LOCF) principle was used.

Third-party observer of participant completes 75-item scale. Comprised of 3 subscales. Each item rated on 3-point Likert scale: 1 (behavior never observed) to 3 (behavior often observed). Global executive composite (GEC) subscale rates participant's GEC in everyday environment (75-225 total score). Behavioral regulation subscale measures participant's control over behavior (30-90 total score). Metacognition subscale assesses systematic problem-solving ability while sustaining these task-completion efforts in active working memory (40-120 total score). Higher subscale ratings indicate greater perceived impairment.

Outcome measures

Measure	Atomoxetine n=148 Participants 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Mean Change From Baseline to 48 Weeks Endpoint in the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) Version: Informant Scores (BRIEF-A:Informant Scores) GEC Subscale Score (n=146)	-8.5 units on a scale Standard Deviation 22.5
Mean Change From Baseline to 48 Weeks Endpoint in the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) Version: Informant Scores (BRIEF-A:Informant Scores) Behavioral Regulation Subscale Score (n=148)	-2.9 units on a scale Standard Deviation 10.0
Mean Change From Baseline to 48 Weeks Endpoint in the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) Version: Informant Scores (BRIEF-A:Informant Scores) Metacognition Subscale Score (n=147)	-5.5 units on a scale Standard Deviation 14.0

SECONDARY outcome

Timeframe: Baseline, 48 weeks

Population: All participants who received at least one dose of study drug, and had a baseline and at least one post-baseline HAMD-17 measurement. Last observation carried forward (LOCF) principle was used.

The HAMD-17 instrument consists of 17 items used to assess the severity of depression and its improvement during the course of therapy. This instrument is completed by the clinician based on his or her assessment of the participant. Each item was evaluated and scored using either a 5-point scale of 0 (not present) to 4 (very severe) or a 3-point scale of 0 (not present) to 2 (marked). The total score is the sum of the scores from HAMD-17 Items 1 through 17 and ranges from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate greater symptom severity.

Outcome measures

Measure	Atomoxetine n=198 Participants 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Mean Change From Baseline to 48 Weeks Endpoint in Comorbid, Depressive Symptoms, as Measured by Hamilton Depression Rating Scale-17 (HAMD-17) Items	0.2 units on a scale Standard Deviation 2.9

Adverse Events

Atomoxetine

Serious events: 5 serious events

Other events: 180 other events

Deaths: 0 deaths

Serious adverse events

Measure	Atomoxetine n=211 participants at risk 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Immune system disorders Anaphylactic reaction	0.47% 1/211 • Number of events 1
Infections and infestations Infectious peritonitis	0.47% 1/211 • Number of events 1
Injury, poisoning and procedural complications Limb traumatic amputation	0.47% 1/211 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	0.47% 1/211 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.47% 1/211 • Number of events 1

Other adverse events

Measure	Atomoxetine n=211 participants at risk 40-120 milligrams/day (mg/day) taken by mouth, once a day for 48 weeks
Cardiac disorders Palpitations	6.6% 14/211 • Number of events 14
Cardiac disorders Tachycardia	5.2% 11/211 • Number of events 11
Gastrointestinal disorders Abdominal discomfort	5.2% 11/211 • Number of events 15
Gastrointestinal disorders Constipation	7.6% 16/211 • Number of events 18
Gastrointestinal disorders Nausea	42.7% 90/211 • Number of events 121
Gastrointestinal disorders Vomiting	6.2% 13/211 • Number of events 29
General disorders Thirst	13.3% 28/211 • Number of events 33
Immune system disorders Seasonal allergy	5.2% 11/211 • Number of events 11
Infections and infestations Nasopharyngitis	31.8% 67/211 • Number of events 100
Metabolism and nutrition disorders Decreased appetite	9.5% 20/211 • Number of events 21
Nervous system disorders Headache	14.7% 31/211 • Number of events 48
Nervous system disorders Somnolence	9.0% 19/211 • Number of events 23

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