Trial Outcomes & Findings for Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (NCT NCT00429273)
NCT ID: NCT00429273
Last Updated: 2021-07-30
Results Overview
The primary clinical efficacy variable for treatment was the ADHD-RS-IV (Attention-Deficit/Hyperactivity Disorder Rating Scale) Total Score and two sub-scales (Inattentive and Hyperactive-Impulsive ). The rating scale has 18 questions with answer options: None (0), Mild (1), Moderate (2) and Severe (3). Min 0; max 3. Scores are obtained by summing each item; The higher the score, the worse the outcome. Total score range: 0-54 Total Inattentive score range: 0-27 Total Hyperactive/Impulsive score range: 0-27
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
212 participants
Primary outcome timeframe
Measured at baseline Week 4 and Week 8
Results posted on
2021-07-30
Participant Flow
212 randomized (deemed eligible and enrolled). 71 randomized to Group 1: 3 dropped prior to receiving drug; thus 68 started drug. 70 randomized to Group 2: 1 dropped before receiving drug; thus 69 started drug. 71 randomized to Group 3:1 dropped before receiving drug; thus 70 started drug.
Participant milestones
| Measure |
Group 1: Guan-Guan+Placebo
weeks 1-4: Guanfacine weeks 5-8: Guanfacine+Placebo
|
Group 2: Placebo-Placebo+DMPH
weeks 1-4: Placebo weeks 5-8: Placebo+DMPH
|
Group 3: Guan-Guan+DMPH
weeks 1-4: Guanfacine weeks 5-8: Guanfacine+DMPH (comb)
|
|---|---|---|---|
|
Overall Study
STARTED
|
68
|
69
|
70
|
|
Overall Study
COMPLETED
|
60
|
61
|
61
|
|
Overall Study
NOT COMPLETED
|
8
|
8
|
9
|
Reasons for withdrawal
| Measure |
Group 1: Guan-Guan+Placebo
weeks 1-4: Guanfacine weeks 5-8: Guanfacine+Placebo
|
Group 2: Placebo-Placebo+DMPH
weeks 1-4: Placebo weeks 5-8: Placebo+DMPH
|
Group 3: Guan-Guan+DMPH
weeks 1-4: Guanfacine weeks 5-8: Guanfacine+DMPH (comb)
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
2
|
|
Overall Study
Physician Decision
|
6
|
5
|
5
|
|
Overall Study
Adverse Event
|
1
|
1
|
2
|
Baseline Characteristics
of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
Baseline characteristics by cohort
| Measure |
Group 1: Guan-Guan+Placebo
n=68 Participants
weeks 1-4: Guanfacine weeks 5-8: Guanfacine +Placebo
|
Group 2: Placebo-Placebo+DMPH
n=69 Participants
weeks 1-4: Placebo weeks 5-8: Placebo+DMPH
|
Group 3: Guan-Guan+DMPH (Comb)
n=70 Participants
weeks 1-4: Guanfacine weeks 5-8: Guanfacine+DMPH (comb)
|
Total
n=207 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
10.1 years
STANDARD_DEVIATION 2.1 • n=5 Participants
|
10.1 years
STANDARD_DEVIATION 2.0 • n=7 Participants
|
9.9 years
STANDARD_DEVIATION 2.2 • n=5 Participants
|
10.0 years
STANDARD_DEVIATION 2.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
142 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
51 Participants
n=5 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
51 Participants
n=7 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
41 Participants
n=5 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
143 Participants
n=4 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
|
Race/Ethnicity, Customized
African American
|
7 Participants
n=5 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
10 Participants
n=7 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
19 Participants
n=5 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
36 Participants
n=4 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
|
Race/Ethnicity, Customized
Asian, Pacific Islander
|
7 Participants
n=5 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
4 Participants
n=7 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
5 Participants
n=5 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
16 Participants
n=4 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
|
Race/Ethnicity, Customized
Other
|
3 Participants
n=5 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
4 Participants
n=7 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
5 Participants
n=5 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
12 Participants
n=4 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
|
Race/Ethnicity, Customized
Hispanic
|
16 Participants
n=5 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
10 Participants
n=7 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
18 Participants
n=5 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
44 Participants
n=4 Participants • of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
|
PRIMARY outcome
Timeframe: Measured at baseline Week 4 and Week 8Population: Every contrast includes estimates of maturation/time trend and the within subject covariance structure based on all participants using full information maximum likelihood estimation.
The primary clinical efficacy variable for treatment was the ADHD-RS-IV (Attention-Deficit/Hyperactivity Disorder Rating Scale) Total Score and two sub-scales (Inattentive and Hyperactive-Impulsive ). The rating scale has 18 questions with answer options: None (0), Mild (1), Moderate (2) and Severe (3). Min 0; max 3. Scores are obtained by summing each item; The higher the score, the worse the outcome. Total score range: 0-54 Total Inattentive score range: 0-27 Total Hyperactive/Impulsive score range: 0-27
Outcome measures
| Measure |
Estimated Difference Between Guan and Placebo
n=207 Participants
Contrasts based on all observations of patients treated with guam and all patients on placebo controlling for time effects. For placebo this included patients in the guan-guan arm at baseline, the guan-combo arm at baseline, and the placebo-DMPH arm at baseline and 4 weeks, while the estimates for guan are based on the guan-guan arm both at 4 weeks and 8 weeks, and the guan-combo arm at 4 weeks only. Participant specific effects and time effects are controlled for based on estimates from all participants and all time points.
|
Estimated Difference Between DMPH and Placebo
n=207 Participants
Contrasts based on all observations of patients treated with dmph and all patients on placebo controlling for time effects. For placebo this included patients in the guan-guan arm at baseline, the guan-combo arm at baseline, and the placebo-DMPH arm at baseline and 4 weeks, while the estimates for DMPH are based on the placebo-guan arm at 8 weeks. Participant specific effects and time effects are controlled for based on estimates from all participants and all time points.
|
Estimated Difference Between Placebo and Combo
n=207 Participants
Contrasts based on all observations of patients treated with combo and all patients on placebo controlling for time effects. For placebo this included patients in the guan-guan arm at baseline, the guan-combo arm at baseline, and the placebo-DMPH arm at baseline and 4 weeks, while the estimates for DMPH are based on the guan-combo arm at 8 weeks. Participant specific effects and time effects are controlled for based on estimates from all participants and all time points.
|
|---|---|---|---|
|
ADHD IV Rating Scale (Attention Deficit Hyperactivity Disorder Rating Scale)
Total ADHD-RS Score
|
-7.77 units on a scale
Standard Error 1.70
|
-7.99 units on a scale
Standard Error 1.22
|
-10.66 units on a scale
Standard Error 1.99
|
|
ADHD IV Rating Scale (Attention Deficit Hyperactivity Disorder Rating Scale)
Inattentive Subscale
|
-4.14 units on a scale
Standard Error 0.99
|
-4.10 units on a scale
Standard Error 0.71
|
-5.89 units on a scale
Standard Error 1.15
|
|
ADHD IV Rating Scale (Attention Deficit Hyperactivity Disorder Rating Scale)
Hyperactive Impulsive Subscale
|
-3.73 units on a scale
Standard Error 0.92
|
-4.0 units on a scale
Standard Error 0.69
|
-5.10 units on a scale
Standard Error 1.12
|
Adverse Events
Group 1: Guan-Guan+Placebo
Serious events: 0 serious events
Other events: 66 other events
Deaths: 0 deaths
Group 2: Placebo-Placebo+DMPH
Serious events: 0 serious events
Other events: 66 other events
Deaths: 0 deaths
Group 3: Guan-Guan+DMPH
Serious events: 0 serious events
Other events: 69 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group 1: Guan-Guan+Placebo
n=68 participants at risk
week 1-4: Guanfacine weeks 5-8: Guanfacine+Placebo
|
Group 2: Placebo-Placebo+DMPH
n=69 participants at risk
week 1-4: Placebo week 5-8: Placebo+DMPH
|
Group 3: Guan-Guan+DMPH
n=70 participants at risk
week 1-4: Guanfacine week 5-8: Guanfacine+DMPH (comb)
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
16.2%
11/68 • Number of events 11
|
14.5%
10/69 • Number of events 10
|
14.3%
10/70 • Number of events 10
|
|
Gastrointestinal disorders
Abdominal Pain
|
27.9%
19/68 • Number of events 19
|
26.1%
18/69 • Number of events 18
|
22.9%
16/70 • Number of events 16
|
|
Psychiatric disorders
Headache
|
50.0%
34/68 • Number of events 34
|
33.3%
23/69 • Number of events 23
|
32.9%
23/70 • Number of events 23
|
|
Psychiatric disorders
Irritability
|
22.1%
15/68 • Number of events 15
|
17.4%
12/69 • Number of events 12
|
25.7%
18/70 • Number of events 18
|
|
Psychiatric disorders
Sedation
|
17.6%
12/68 • Number of events 12
|
5.8%
4/69 • Number of events 4
|
22.9%
16/70 • Number of events 16
|
|
Psychiatric disorders
Somnolence
|
23.5%
16/68 • Number of events 16
|
4.3%
3/69 • Number of events 3
|
21.4%
15/70 • Number of events 15
|
|
Psychiatric disorders
Affect Lability
|
10.3%
7/68 • Number of events 7
|
20.3%
14/69 • Number of events 14
|
11.4%
8/70 • Number of events 8
|
|
General disorders
Insomnia
|
26.5%
18/68 • Number of events 18
|
29.0%
20/69 • Number of events 20
|
34.3%
24/70 • Number of events 24
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
22.1%
15/68 • Number of events 15
|
44.9%
31/69 • Number of events 31
|
35.7%
25/70 • Number of events 25
|
|
General disorders
Lethargy
|
33.8%
23/68 • Number of events 23
|
13.0%
9/69 • Number of events 9
|
22.9%
16/70 • Number of events 16
|
|
General disorders
Fatigue
|
32.4%
22/68 • Number of events 22
|
7.2%
5/69 • Number of events 5
|
17.1%
12/70 • Number of events 12
|
|
Vascular disorders
Dizziness
|
11.8%
8/68 • Number of events 8
|
8.7%
6/69 • Number of events 6
|
10.0%
7/70 • Number of events 7
|
Additional Information
James T. McCracken, M.D.
University of California, Los Angeles
Phone: 310-825-0470
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place