Trial Outcomes & Findings for Atomoxetine, Placebo and Parent Management Training in Autism (NCT NCT00844753)
NCT ID: NCT00844753
Last Updated: 2016-02-04
Results Overview
Respondents were defined as having ≥30% decrease on the SNAP and CGI-I\<=2). The Swanson, Nolan, and Pelham (SNAP)-IV Parent and Teacher Rating Scales were used to measure ADHD and oppositional symptoms at home and school. The SNAP-IV ADHD section contains items for each of the 18 Diagnostic and Statistical Manual of Mental Disorders-IV symptoms of ADHD rated from 0 (not at all) to 3 (very much). The Clinical Global Impressions Scale (CGI) includes subscales for severity of illness and global improvement. The Severity scale is scored from 1 (normal) to 7 (extremely ill), with a rating of ≥4 required for inclusion. The Improvement score ranged from 1 (very much improved) through 4 (no change) to 7 (very much worse). The CGI was completed by a blinded rater based on parent/child interview and review of completed parent and school behavior problem questionnaires at each study visit.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
128 participants
Primary outcome timeframe
week 10
Results posted on
2016-02-04
Participant Flow
200 participants were screened. 131 passed screening. Participants failed screening for the following reasons: 16 Attention Deficit Hyperactivity Disorder (ADHD) not confirmed, 23 Autism Spectrum Disorder not confirmed, 7 previous parent therapy or mental age too low, 23 for other reasons.
Two participants who passed screening withdrew and one child became ineligible because of ADHD severity declining at baseline.
Participant milestones
| Measure |
Atomoxetine (ATX) + Parent Management Training
ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to adverse events. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.
Parent Management Training (PT)-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.
|
Atomoxetine (ATX) Without Parent Management Training
ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.
|
Placebo + Parent Management Training
Sugar pill administered twice daily
Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.
|
Placebo Without Parent Management Training
Sugar pill administered twice daily.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
32
|
32
|
32
|
32
|
|
Overall Study
COMPLETED
|
24
|
29
|
25
|
21
|
|
Overall Study
NOT COMPLETED
|
8
|
3
|
7
|
11
|
Reasons for withdrawal
| Measure |
Atomoxetine (ATX) + Parent Management Training
ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to adverse events. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.
Parent Management Training (PT)-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.
|
Atomoxetine (ATX) Without Parent Management Training
ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.
|
Placebo + Parent Management Training
Sugar pill administered twice daily
Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.
|
Placebo Without Parent Management Training
Sugar pill administered twice daily.
|
|---|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
2
|
2
|
|
Overall Study
Adverse Event
|
3
|
2
|
5
|
5
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
0
|
1
|
|
Overall Study
could not swallow medication
|
2
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
3
|
Baseline Characteristics
Atomoxetine, Placebo and Parent Management Training in Autism
Baseline characteristics by cohort
| Measure |
Atomoxetine + Parent Management Training
n=32 Participants
ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.
Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.
|
Atomoxetine Without Parent Management Training
n=32 Participants
ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.
|
Placebo + Parent Management Training
n=32 Participants
Sugar pill administered twice daily
Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.
|
Placebo Without Parent Management Training
n=32 Participants
Sugar pill administered twice daily.
|
Total
n=128 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
8.0 years
STANDARD_DEVIATION 1.9 • n=93 Participants
|
8.6 years
STANDARD_DEVIATION 2.3 • n=4 Participants
|
7.7 years
STANDARD_DEVIATION 1.5 • n=27 Participants
|
8.2 years
STANDARD_DEVIATION 2.4 • n=483 Participants
|
8.1 years
STANDARD_DEVIATION 2.1 • n=36 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
20 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
27 Participants
n=27 Participants
|
24 Participants
n=483 Participants
|
108 Participants
n=36 Participants
|
|
Region of Enrollment
United States
|
32 participants
n=93 Participants
|
32 participants
n=4 Participants
|
32 participants
n=27 Participants
|
32 participants
n=483 Participants
|
128 participants
n=36 Participants
|
PRIMARY outcome
Timeframe: week 10Respondents were defined as having ≥30% decrease on the SNAP and CGI-I\<=2). The Swanson, Nolan, and Pelham (SNAP)-IV Parent and Teacher Rating Scales were used to measure ADHD and oppositional symptoms at home and school. The SNAP-IV ADHD section contains items for each of the 18 Diagnostic and Statistical Manual of Mental Disorders-IV symptoms of ADHD rated from 0 (not at all) to 3 (very much). The Clinical Global Impressions Scale (CGI) includes subscales for severity of illness and global improvement. The Severity scale is scored from 1 (normal) to 7 (extremely ill), with a rating of ≥4 required for inclusion. The Improvement score ranged from 1 (very much improved) through 4 (no change) to 7 (very much worse). The CGI was completed by a blinded rater based on parent/child interview and review of completed parent and school behavior problem questionnaires at each study visit.
Outcome measures
| Measure |
Atomoxetine + Parent Management Training
n=32 Participants
ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.
Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.
|
Atomoxetine Without Parent Management Training
n=32 Participants
ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.
|
Placebo + Parent Management Training
n=32 Participants
Sugar pill administered twice daily
Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.
|
Placebo Without Parent Management Training
n=32 Participants
Sugar pill administered twice daily.
|
|---|---|---|---|---|
|
Percentage of Participants Who Were Attention Deficit Hyperactivity Disorder (ADHD) Respondents
|
45.2 percentage of participants
|
46.9 percentage of participants
|
29.0 percentage of participants
|
19.4 percentage of participants
|
PRIMARY outcome
Timeframe: week 10Respondents were defined as having ≥30% decrease on the HSQ and CGI-I≤2). The 25-item HSQ was adapted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate behavioral noncompliance in children with autism spectrum disorder (ASD). The Home Situations Questionnaire - Pervasive Developmental Disorder (HSQ) is a 25-item parent rating scale assessing noncompliance. Parents are asked to indicate whether each item is a problem and, if so, its severity from 1 (mild) to 9 (severe). The School Situations Questionnaire (SSQ) is a 9-item teacher rating scale that assesses noncompliance. The SSQ is a companion instrument to the HSQ and uses the same rating scale. The Clinical Global Impressions Scale (CGI) includes subscales for severity of illness and global improvement. The Severity scale is scored from 1 (normal) to 7 (extremely ill),
Outcome measures
| Measure |
Atomoxetine + Parent Management Training
n=32 Participants
ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.
Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.
|
Atomoxetine Without Parent Management Training
n=32 Participants
ATX doses were split twice daily to prevent side effects. However, once-daily dosing was allowed if strongly preferred by a given family. ATX doses were individually adjusted according to a weight-based dosage schedule, with medical clinicians allowed to delay increases or to reduce doses due to AEs. The initial dose was 0.3 mg/kg/day (rounded to the nearest 5 mg) with weekly escalations by 0.3 mg/kg/day, unless there were limiting side effects or no further room for improvement, to a target dose of 1.2 mg/kg/day, and could be increased to a maximum of 1.8 mg/kg/day based on clinical status and response.
|
Placebo + Parent Management Training
n=32 Participants
Sugar pill administered twice daily
Parent Management Training-Families assigned to PT met weekly for individual sessions with a PT clinician. Sessions were adapted from the RUPP Parent Training Manual and covered topics such as preventing behavior problems, reinforcement, time out, and planned ignoring. Each session lasted 60 to 90 minutes and included didactic materials, videos, and role playing.
|
Placebo Without Parent Management Training
n=32 Participants
Sugar pill administered twice daily.
|
|---|---|---|---|---|
|
Percentage of Participants Who Were Autism Spectrum Disorder Respondents
|
22.6 percentage of participants
|
43.8 percentage of participants
|
38.7 percentage of participants
|
16.4 percentage of participants
|
Adverse Events
Atomoxetine
Serious events: 0 serious events
Other events: 59 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 61 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Atomoxetine
n=63 participants at risk
Data includes both the ATX alone arm and the ATX+ parent therapy arm
|
Placebo
n=62 participants at risk
Data includes the placebo alone arm and the placebo+parent therapy arm
|
|---|---|---|
|
Psychiatric disorders
Irritability
|
42.9%
27/63 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
46.8%
29/62 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
47.6%
30/63 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
29.0%
18/62 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
|
Psychiatric disorders
Agitation
|
30.2%
19/63 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
32.3%
20/62 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
|
General disorders
Difficulty sleeping
|
30.2%
19/63 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
17.7%
11/62 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
|
Gastrointestinal disorders
Vomiting
|
22.2%
14/63 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
16.1%
10/62 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
|
Gastrointestinal disorders
Constipation
|
11.1%
7/63 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
14.5%
9/62 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
|
Gastrointestinal disorders
Abdominal pain
|
15.9%
10/63 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
4.8%
3/62 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
|
Gastrointestinal disorders
Diarrhea
|
4.8%
3/63 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
6.5%
4/62 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
|
Psychiatric disorders
Aggression
|
3.2%
2/63 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
6.5%
4/62 • 10 weeks
Only AEs related to study drug were assessed. Therefore AEs are presented for subjects on ATX or on placebo and not by arm. AEs were assessed for subjects taking at least one week of treatment. One participant in the ATX arm and two participants in the placebo arm did not take treatment for at least one week.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place