Trial Outcomes & Findings for Effect of Guanfacine Extended-Release on Attention Deficit Hyperactivity Disorder (ADHD)-Associated Insomnia (NCT NCT01156051)
NCT ID: NCT01156051
Last Updated: 2014-08-11
Results Overview
Change in objective measures of sleep, using polysomnography
TERMINATED
PHASE4
29 participants
Baseline to last observation carried forward (after at least one week of dose stability)
2014-08-11
Participant Flow
From 2010 to 2012, children were referred primarily from the outpatient practice affiliated with a community based hospital dedicated to the evaluation and management of children with special needs. Four patients were referred from community pediatricians who commonly refer to the practice.
Medications for ADHD, that would affect sleep/alertness, or that had psychoactive properties were discontinued prior to polysomnography. Of the 35 who entered screening, 29 were enrolled. Children were disquialified for not meeting diagnostic criteria or for having disqualifying conditions (e.g., depression, heart pathology).
Participant milestones
| Measure |
Treatment Group
Children who received (double blinded, randomized) guanfacine extended release tablets in a flexible dosing protocol, with doses ranging from 1mg to 4mg administered once daily in the morning.
|
Control
Children who received a matching placebo tablet administered once daily in the morning in a flexible dosing protocol, with tablets identical to guanfacine extended release from 1mg to 4mg.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
17
|
|
Overall Study
COMPLETED
|
11
|
16
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Treatment Group
Children who received (double blinded, randomized) guanfacine extended release tablets in a flexible dosing protocol, with doses ranging from 1mg to 4mg administered once daily in the morning.
|
Control
Children who received a matching placebo tablet administered once daily in the morning in a flexible dosing protocol, with tablets identical to guanfacine extended release from 1mg to 4mg.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
patient not compliant with protocol
|
0
|
1
|
Baseline Characteristics
Effect of Guanfacine Extended-Release on Attention Deficit Hyperactivity Disorder (ADHD)-Associated Insomnia
Baseline characteristics by cohort
| Measure |
Guanfacine Extended-Release Tablets
n=11 Participants
Guanfacine Extended-Release Tablets 1mg, 2mg, 3mg, and 4mg
Guanfacine extended-release tablets: Guanfacine extended-release tablets were started at 1mg and then increased at weekly intervals to 2mg, 3mg, or 4mg as needed and as tolerated
|
Placebo Comparator
n=16 Participants
Placebo control
Placebo comparator: Placebo tablets identical to the experimental arm guanfacine extended-release tablets 1mg were started and then increased at weekly intervals to 2mg, 3mg, or 4mg as needed and as tolerated
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
9.1 years
STANDARD_DEVIATION 1.8 • n=99 Participants
|
8.8 years
STANDARD_DEVIATION 1.9 • n=107 Participants
|
8.9 years
STANDARD_DEVIATION 1.9 • n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
10 participants
n=99 Participants
|
12 participants
n=107 Participants
|
22 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
African-American
|
1 participants
n=99 Participants
|
4 participants
n=107 Participants
|
5 participants
n=206 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=99 Participants
|
16 participants
n=107 Participants
|
27 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline to last observation carried forward (after at least one week of dose stability)Population: 29 children were enrolled, one (treatment) was lost to follow up an one (placebo) was discontinued due to noncompliance with protocol.
Change in objective measures of sleep, using polysomnography
Outcome measures
| Measure |
Guanfacine Extended-Release Tablets
n=11 Participants
Guanfacine Extended-Release Tablets 1mg, 2mg, 3mg, and 4mg
Guanfacine extended-release tablets: Guanfacine extended-release tablets will be started at 1mg and then increased at weekly intervals to 2mg, 3mg, or 4mg as needed and as tolerated
|
Placebo Comparator
n=16 Participants
Placebo control
Placebo comparator: Placebo tablets identical to the experimental arm guanfacine extended-release tablets 1mg, 2mg, 3mg, 4mg, but without the active ingredient (guanfacine).
|
|---|---|---|
|
Change in Polysomnographic Total Sleep Time (TST)
|
-57.32 minutes
Standard Deviation 89.17
|
31.32 minutes
Standard Deviation 59.54
|
SECONDARY outcome
Timeframe: Baseline to last observation carried forward (after at least one week of dose stability)Population: 29 children enrolled, but two were discontinued before termination data was available: one (treatment) was lost to follow up and one (placebo) was noncompliant with the protocol.
Change in baseline to treatment ADHD-Rating Scale IV (Investigator-interview ) total. This scale quantitates ADHD symptoms based on DSM-IV criteria with a minimum score of 0 and a maximum score of 54 (higher scores suggesting more ADHD symptoms). The total score is a sum of the 9 items on the ADHD Rating Scale IV inattention score and the 9 items on the ADHD Rating Scale IV hyperactivity-impulsivity score (scores for each 0-27).
Outcome measures
| Measure |
Guanfacine Extended-Release Tablets
n=11 Participants
Guanfacine Extended-Release Tablets 1mg, 2mg, 3mg, and 4mg
Guanfacine extended-release tablets: Guanfacine extended-release tablets will be started at 1mg and then increased at weekly intervals to 2mg, 3mg, or 4mg as needed and as tolerated
|
Placebo Comparator
n=16 Participants
Placebo control
Placebo comparator: Placebo tablets identical to the experimental arm guanfacine extended-release tablets 1mg, 2mg, 3mg, 4mg, but without the active ingredient (guanfacine).
|
|---|---|---|
|
Change in Baseline to Treatment ADHD-Rating Scale IV Total Score
|
-18.27 units on a scale
Standard Deviation 11.31
|
-1.69 units on a scale
Standard Deviation 9.16
|
SECONDARY outcome
Timeframe: Baseline to last observation carried forward (after at least one week of dose stability)Population: 29 children were enrolled; two were disqualified: one (treatment) was lost to follow-up,and one (placebo) was noncompliant with the protocol.
Change in an objective measure of sleep onset, using polysomnography.
Outcome measures
| Measure |
Guanfacine Extended-Release Tablets
n=11 Participants
Guanfacine Extended-Release Tablets 1mg, 2mg, 3mg, and 4mg
Guanfacine extended-release tablets: Guanfacine extended-release tablets will be started at 1mg and then increased at weekly intervals to 2mg, 3mg, or 4mg as needed and as tolerated
|
Placebo Comparator
n=16 Participants
Placebo control
Placebo comparator: Placebo tablets identical to the experimental arm guanfacine extended-release tablets 1mg, 2mg, 3mg, 4mg, but without the active ingredient (guanfacine).
|
|---|---|---|
|
Change in Baseline to Treatment Latency to Persistent Sleep (LPS)
|
10.54 minutes
Standard Deviation 88.44
|
-19.94 minutes
Standard Deviation 54.12
|
SECONDARY outcome
Timeframe: Baseline to last observation carried forward (after at least one week of dose stability)Population: 29 children were enrolled; two were disqualified: one (treatment) was lost to follow-up,and one (placebo) was noncompliant with the protocol.
Polysomnographic parameter of sleep assessing how many minutes of wakefulness occurred after sleep onset and before full morning awakening.
Outcome measures
| Measure |
Guanfacine Extended-Release Tablets
n=11 Participants
Guanfacine Extended-Release Tablets 1mg, 2mg, 3mg, and 4mg
Guanfacine extended-release tablets: Guanfacine extended-release tablets will be started at 1mg and then increased at weekly intervals to 2mg, 3mg, or 4mg as needed and as tolerated
|
Placebo Comparator
n=16 Participants
Placebo control
Placebo comparator: Placebo tablets identical to the experimental arm guanfacine extended-release tablets 1mg, 2mg, 3mg, 4mg, but without the active ingredient (guanfacine).
|
|---|---|---|
|
Change in Baseline to Treatment Minutes of Wake Time After Sleep Onset (WASO)
|
21.80 minutes
Standard Deviation 18.51
|
-3.90 minutes
Standard Deviation 17.20
|
Adverse Events
Guanfacine Extended-Release Tablets
Placebo Comparator
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Guanfacine Extended-Release Tablets
n=12 participants at risk
Guanfacine Extended-Release Tablets 1mg, 2mg, 3mg, and 4mg
Guanfacine extended-release tablets: Guanfacine extended-release tablets will be started at 1mg and then increased at weekly intervals to 2mg, 3mg, or 4mg as needed and as tolerated
|
Placebo Comparator
n=17 participants at risk
Placebo control
Placebo comparator: Placebo tablets identical to the experimental arm guanfacine extended-release tablets 1mg, 2mg, 3mg, 4mg, but without the active ingredient (guanfacine).
|
|---|---|---|
|
Nervous system disorders
somnolence / sedation
|
66.7%
8/12 • Number of events 8
|
5.9%
1/17 • Number of events 1
|
|
Nervous system disorders
headache
|
33.3%
4/12 • Number of events 4
|
11.8%
2/17 • Number of events 2
|
|
Gastrointestinal disorders
stomachache / abdominal pain
|
8.3%
1/12 • Number of events 1
|
11.8%
2/17 • Number of events 2
|
|
Gastrointestinal disorders
acute gastroenteritis
|
8.3%
1/12 • Number of events 1
|
11.8%
2/17 • Number of events 2
|
|
Metabolism and nutrition disorders
decreased appetite
|
0.00%
0/12
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
inguinal hernia
|
0.00%
0/12
|
5.9%
1/17 • Number of events 1
|
|
Infections and infestations
febrile illness
|
8.3%
1/12 • Number of events 1
|
0.00%
0/17
|
|
Infections and infestations
upper respiratory infection
|
25.0%
3/12 • Number of events 3
|
17.6%
3/17 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
exacerbation of allergic rhinitis
|
8.3%
1/12 • Number of events 1
|
29.4%
5/17 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
exacerbation of asthma
|
0.00%
0/12
|
5.9%
1/17 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
8.3%
1/12 • Number of events 1
|
0.00%
0/17
|
|
Renal and urinary disorders
enuresis
|
8.3%
1/12 • Number of events 1
|
0.00%
0/17
|
|
Nervous system disorders
dizziness
|
8.3%
1/12 • Number of events 1
|
0.00%
0/17
|
|
Musculoskeletal and connective tissue disorders
musculoskeletal chest pain
|
8.3%
1/12 • Number of events 1
|
0.00%
0/17
|
|
General disorders
oral pain due to loose teeth
|
8.3%
1/12 • Number of events 1
|
0.00%
0/17
|
|
Skin and subcutaneous tissue disorders
dermatitis
|
8.3%
1/12 • Number of events 1
|
11.8%
2/17 • Number of events 2
|
|
Psychiatric disorders
stuttering
|
0.00%
0/12
|
5.9%
1/17 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place