Trial Outcomes & Findings for Impact of Strattera and Behavior Therapy on the Home and School Functioning of Children With ADHD (NCT NCT00918567)

NCT ID: NCT00918567

Last Updated: 2020-10-20

Results Overview

Observations were conducted using the Student Behavior Teacher Response Observation Code. After learning the classroom rules, observers watched children in their classrooms for 30 minutes during an academic activity and recorded each time the subject violated a classroom rule. Total classroom rule violations were used as the primary outcome measures for the study.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 56 participants
• Primary outcome timeframe: Endpoint (Week 8)
• Results posted on: 2020-10-20

Participant Flow

Subjects were recruited from schools, pediatric offices and the local community through radio and print advertisement. Subjects were recruited between Jan of 2007 and the spring of 2008.

uneven number because set of twins randomized as one unit at parental request

Participant milestones

Measure	Combined Therapy atomoxetine plus behavior therapy	Drug Therapy atomoxetine alone
Overall Study STARTED	29	27
Overall Study COMPLETED	24	25
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Measure	Combined Therapy atomoxetine plus behavior therapy	Drug Therapy atomoxetine alone
Overall Study Lack of Efficacy	3	1
Overall Study Withdrawal by Subject	1	1
Overall Study Adverse Event	1	0

Baseline Characteristics

Impact of Strattera and Behavior Therapy on the Home and School Functioning of Children With ADHD

Baseline characteristics by cohort

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone	Total n=56 Participants Total of all reporting groups
Age, Categorical <=18 years	29 Participants n=5 Participants	27 Participants n=7 Participants	56 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	8.3 years STANDARD_DEVIATION 1.6 • n=5 Participants	8.9 years STANDARD_DEVIATION 1.5 • n=7 Participants	8.59 years STANDARD_DEVIATION 1.581 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	21 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment United States	29 participants n=5 Participants	27 participants n=7 Participants	56 participants n=5 Participants

PRIMARY outcome

Timeframe: Endpoint (Week 8)

Population: all subjects analyzed using ITT

Observations were conducted using the Student Behavior Teacher Response Observation Code. After learning the classroom rules, observers watched children in their classrooms for 30 minutes during an academic activity and recorded each time the subject violated a classroom rule. Total classroom rule violations were used as the primary outcome measures for the study.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
Rule Violations During Direct Classroom Observation at Endpoint (Week 8)	6.15 number occurences per 30 mins Standard Error 1.37	4.93 number occurences per 30 mins Standard Error 1.36

SECONDARY outcome

Timeframe: Endpoint (Week 8)

Population: Intent to treat

The IRS is a 8 item measure that uses visual-analogue scales to evaluate the child's problem level and need for treatment in developmentally important areas, such as peer relationships, adult-child relationships, academic performance, and classroom behavior 51. The scale is scored from 0 (no problem) to 6 (extreme problem). The scale has excellent test-retest and inter-rater reliability and well supported validity 51, 52.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
Impairment Rating Scale (Parent Completed) at Endpoint	2.66 units on a scale Standard Error .37	2.84 units on a scale Standard Error .36

SECONDARY outcome

Timeframe: Endpoint (Week 8)

Population: ITT was used

The IRS is a 6 item measure that uses visual-analogue scales to evaluate the child's problem level and need for treatment in developmentally important areas, such as peer relationships, adult-child relationships, academic performance, and classroom behavior. The scale is scored from 0 (no problem) to 6 (extreme problem). The scale has excellent test-retest and inter-rater reliability and well supported validity.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
Impairment Rating Scale (Teachers) at Endpoint	2.02 units on a scale Standard Error 0.42	2.29 units on a scale Standard Error 0.43

SECONDARY outcome

Timeframe: Endpoint (Week 8)

Population: ITT was used

The PSERS measures adverse events commonly associated with stimulant medication and has been used in multiple studies of ADHD. For this study, the PSERS was modified to also assess adverse emotional events potentially associated with ATX, including suicidal statements. The resulting scale consisted of 14 items (an additional sleep item for parents) rated from 0 ("none") to 3 ("severe"). An overall side effects score was computed by averaging across all ratings and used in analyses.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
Pittsburgh Side Effects Rating Scale (PSERS)(Parent Completed) at Endpoint:	.38 units on a scale Standard Error .06	.34 units on a scale Standard Error .06

SECONDARY outcome

Timeframe: at weeks 8 (Endpoint)

Population: ITT was used

The PSERS measures adverse events commonly associated with stimulant medication and has been used in multiple studies of ADHD. For this study, the PSERS was modified to also assess adverse emotional events potentially associated with ATX, including suicidal statements. The resulting scale consisted of 13 items (for teachers) rated from 0 ("none") to 3 ("severe"). An overall side effects score was computed by averaging across all ratings and used in analyses.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
Pittsburgh Side Effects Rating Scale (PSERS)(Teacher Rated):	.23 units on a scale Standard Error .05	.21 units on a scale Standard Error .05

SECONDARY outcome

Timeframe: Endpoint (Week 8)

Population: ITT was used

The DBD consists of 8 items that are the DSM-IV symptoms of Oppositional Defiant Disorder (ODD). Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
Disruptive Behavior Disorders Rating Scale ODD Subscale (DBD- Parent Completed) at Endpoint	.90 units on a scale Standard Error .13	1.12 units on a scale Standard Error .13

SECONDARY outcome

Timeframe: Endpoint (Week 8)

Population: ITT was used

The DBD consists of 8 items that are the DSM-IV symptoms of Oppositional Defiant Disorder (ODD). Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
Disruptive Behavior Disorder Rating Scale ODD Subscale(DBD- Teacher Completed) at Endpoint	.54 units on a scale Standard Error .15	.71 units on a scale Standard Error .14

SECONDARY outcome

Timeframe: Endpoint (Week 8)

Population: ITT was used

completed by parents to measure children's problem behaviors (PB). Items are rated from 0 ("not at all") to 2 ("very often"). The scale has 55 items. The score reported below is the sum total of the items on the scale and then averaged for the whole group. Therefore, the range can be between 0 and 110. A higher score indicates a better outcome.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
Social Skills Rating Scale Problem Behavior Subscale(SSRS Parent) at Endpoint	16.48 units on a scale Standard Error 1.21	19.53 units on a scale Standard Error 1.19

SECONDARY outcome

Timeframe: Endpoint (Week 8)

Population: ITT was used

The SSRS was completed by teachers to measure children's problem behaviors (PB). Items are rated from 0 ("not at all") to 2 ("very often"). The scale has 55 items. The score reported below is the sum total of the items on the scale and then averaged for the whole group. Therefore, the range can be between 0 and 110. A higher score indicates a better outcome.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
Social Skills Rating Scale Problem Behavior Subscale(SSRS Teachers) at Endpoint	13.88 units on a scale Standard Error 1.25	13.96 units on a scale Standard Error 1.29

SECONDARY outcome

Timeframe: Endpoint (Week 8)

Population: Intent to treat

The DBD consists of 18 items that are the DSM-IV symptoms of ADHD. Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
ADHD Subscale of the DBD (Parent Completed) at Endpoint	1.07 units on a scale Standard Deviation 0.11	1.47 units on a scale Standard Deviation 0.11

SECONDARY outcome

Timeframe: Endpoint (Week 8)

Population: ITT used

The ADHD subscale of the DBD consists of 18 items that are the DSM-IV symptoms of ADHD. Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies.

Outcome measures

Measure	Combined Therapy n=29 Participants atomoxetine plus behavior therapy	Drug Therapy n=27 Participants atomoxetine alone
ADHD Subscale of the DBD (Teacher Completed) at Endpoint	1.01 units on a scale Standard Error 0.13	1.13 units on a scale Standard Error 0.13

Adverse Events

Combined Therapy

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Drug Therapy

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Combined Therapy n=29 participants at risk atomoxetine plus behavior therapy	Drug Therapy n=27 participants at risk atomoxetine alone
Psychiatric disorders Trouble Sleeping	13.8% 4/29 • Number of events 6 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	11.1% 3/27 • Number of events 4 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
Gastrointestinal disorders stomachaches	27.6% 8/29 • Number of events 10 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	14.8% 4/27 • Number of events 7 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
Metabolism and nutrition disorders appetite loss	24.1% 7/29 • Number of events 11 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	7.4% 2/27 • Number of events 4 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
Nervous system disorders headaches	17.2% 5/29 • Number of events 6 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	11.1% 3/27 • Number of events 5 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
Nervous system disorders motor tics	13.8% 4/29 • Number of events 7 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	57.1% 4/7 • Number of events 7 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
Psychiatric disorders picking at skin	31.0% 9/29 • Number of events 16 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	37.0% 10/27 • Number of events 17 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
Psychiatric disorders anxiety	34.5% 10/29 • Number of events 18 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	44.4% 12/27 • Number of events 14 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
Psychiatric disorders dulled/tired looking	44.8% 13/29 • Number of events 15 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	37.0% 10/27 • Number of events 11 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
Psychiatric disorders crabby/irritable	48.3% 14/29 • Number of events 19 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	40.7% 11/27 • Number of events 16 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
Psychiatric disorders depressed mood/crying episodes	27.6% 8/29 • Number of events 12 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	18.5% 5/27 • Number of events 6 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
Psychiatric disorders withdrawn from others	17.2% 5/29 • Number of events 10 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).	11.1% 3/27 • Number of events 5 • The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8. Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).

Additional Information

James Waxmonsky M.D.

SUNY Buffalo

Phone: 305 348 3258

Email: jwaxmons@fiu.edu

Results disclosure agreements

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