Trial Outcomes & Findings for Safety, Tolerability and Efficacy of SPD503 in Treating ADHD in Children Aged 6-17 (NCT NCT00150592)
NCT ID: NCT00150592
Last Updated: 2021-06-10
Results Overview
Choice reaction time (CRT) is a computerized assessment that trains the subject in holding down a press-pad and releasing the press-pad in response to stimuli presented on the screen. The task requires the subject to react as soon as a yellow dot appears in one of five locations, and the subject must respond by lifting their hand from the press-pad. This is the reaction time (RT) and ranges from 100 to 5000 msec. Lower scores indicate better performance.
COMPLETED
PHASE2
182 participants
Baseline and 6 weeks
2021-06-10
Participant Flow
A total of 182 subjects were enrolled. Four (4) subjects were terminated prior to receiving study medication. Thus, 178 were randomized and received study medication.
Participant milestones
| Measure |
SPD503
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
121
|
57
|
|
Overall Study
COMPLETED
|
114
|
54
|
|
Overall Study
NOT COMPLETED
|
7
|
3
|
Reasons for withdrawal
| Measure |
SPD503
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
|
Overall Study
Non-compliance
|
1
|
0
|
Baseline Characteristics
Safety, Tolerability and Efficacy of SPD503 in Treating ADHD in Children Aged 6-17
Baseline characteristics by cohort
| Measure |
SPD503
n=121 Participants
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=57 Participants
|
Total
n=178 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
121 Participants
n=93 Participants
|
57 Participants
n=4 Participants
|
178 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Continuous
|
12.6 years
STANDARD_DEVIATION 2.83 • n=93 Participants
|
12.8 years
STANDARD_DEVIATION 2.77 • n=4 Participants
|
12.6 years
STANDARD_DEVIATION 2.81 • n=27 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
54 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
80 Participants
n=93 Participants
|
44 Participants
n=4 Participants
|
124 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
121 Participants
n=93 Participants
|
57 Participants
n=4 Participants
|
178 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline and 6 weeksPopulation: Per protocol (PP) defined as all subjects who completed the study and were deemed to be protocol-compliant.
Choice reaction time (CRT) is a computerized assessment that trains the subject in holding down a press-pad and releasing the press-pad in response to stimuli presented on the screen. The task requires the subject to react as soon as a yellow dot appears in one of five locations, and the subject must respond by lifting their hand from the press-pad. This is the reaction time (RT) and ranges from 100 to 5000 msec. Lower scores indicate better performance.
Outcome measures
| Measure |
SPD503
n=80 Participants
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=35 Participants
|
|---|---|---|
|
Change From Baseline in Choice Reaction Time (CRT) at 6 Weeks
|
20.7 msec
Standard Deviation 63.11
|
21.9 msec
Standard Deviation 64.04
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksPopulation: PP
The Digital Symbol Substitution Task/Coding Test (DSST/Coding) assesses relative contributions of speed, memory, and visual scanning. Subjects are required to copy symbols that are paired with simple geometric shapes or numbers within a specific time. Scores range from 0-65 in age category 6-7 years and 0-199 in age category 8-17 years. Higher scores indicate better performance.
Outcome measures
| Measure |
SPD503
n=77 Participants
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=34 Participants
|
|---|---|---|
|
Change From Baseline in Digital Symbol Substitution Task/Coding Test (DSST/Coding) Scores at 6 Weeks in Age Category 8-17 Years
|
18.3 Units on a scale
Standard Deviation 14.03
|
20.7 Units on a scale
Standard Deviation 17.18
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksPopulation: PP
The Digital Symbol Substitution Task/Coding Test (DSST/Coding) assesses relative contributions of speed, memory, and visual scanning. Subjects are required to copy symbols that are paired with simple geometric shapes or numbers within a specific time. Scores range from 0-65 in age category 6-7 years and 0-199 in age category 8-17 years. Higher scores indicate better performance.
Outcome measures
| Measure |
SPD503
n=3 Participants
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=1 Participants
|
|---|---|---|
|
Change From Baseline in DSST/Coding Scores at 6 Weeks in Age Category 6-7 Years
|
1.9 Units on a scale
Standard Deviation 1.95
|
9.7 Units on a scale
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksPopulation: PP
The Spatial Working Memory (SWM) Test is a computerized assessment of working memory and strategy performance. The subject is required to find blue "tokens" in various displayed boxes and use the "tokens" to fill a column on the right side of the screen. Subjects can only find "tokens" in new boxes, therefore they must remember where previous "tokens" were found. SWM scores including number of between errors, number of within errors, and number of double errors range 0-800 and SWM strategy scores range 8-56. Lower scores indicate better performance.
Outcome measures
| Measure |
SPD503
n=80 Participants
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=35 Participants
|
|---|---|---|
|
Change From Baseline in Spatial Working Memory (SWM) Scores at 6 Weeks
Between errors
|
-4.4 Units on a scale
Standard Deviation 7.42
|
-3.2 Units on a scale
Standard Deviation 6.75
|
|
Change From Baseline in Spatial Working Memory (SWM) Scores at 6 Weeks
Within errors
|
0.0 Units on a scale
Standard Deviation 1.11
|
-0.1 Units on a scale
Standard Deviation 0.73
|
|
Change From Baseline in Spatial Working Memory (SWM) Scores at 6 Weeks
Double errors
|
-0.0 Units on a scale
Standard Deviation 0.69
|
0.1 Units on a scale
Standard Deviation 0.53
|
|
Change From Baseline in Spatial Working Memory (SWM) Scores at 6 Weeks
Strategy
|
-0.9 Units on a scale
Standard Deviation 2.74
|
-0.1 Units on a scale
Standard Deviation 2.56
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksPopulation: Full Analysis Set (FAS) defined as all subjects who received at least one dose of investigational product.
Change in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth edition (ADHD-RS-IV) total score from baseline. The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54.
Outcome measures
| Measure |
SPD503
n=121 Participants
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=57 Participants
|
|---|---|---|
|
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at 6 Weeks
|
-8.8 Units on a Scale
Standard Deviation 5.98
|
-5.5 Units on a Scale
Standard Deviation 7.23
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: FAS
Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Outcome measures
| Measure |
SPD503
n=121 Participants
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=57 Participants
|
|---|---|---|
|
Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) at 6 Weeks
|
67 Participants
|
20 Participants
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksPopulation: FAS
The Pediatric Daytime Sleepiness Scale (PDSS) is an 8 question questionnaire scored on a scale from 0 (never) to 4 (always). Total scores range from 0 to 32, with increasing score reflecting greater sleepiness.
Outcome measures
| Measure |
SPD503
n=121 Participants
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=57 Participants
|
|---|---|---|
|
Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Scores at 6 Weeks
|
-1.3 Units on a Scale
Standard Deviation 5.36
|
0.9 Units on a Scale
Standard Deviation 5.31
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksPopulation: FAS
The Pictorial Sleepiness Scale (PSS) scores range from 1 (far left wide awake face) to 5 (far right very sleepy face). Increasing score reflects greater sleepiness.
Outcome measures
| Measure |
SPD503
n=121 Participants
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=57 Participants
|
|---|---|---|
|
Change From Baseline in Pictorial Sleepiness Scale (PSS) Scores at 6 Weeks
|
0.0 Units on a Scale
Standard Deviation 0.61
|
0.1 Units on a Scale
Standard Deviation 0.63
|
Adverse Events
SPD503
Placebo
Serious adverse events
| Measure |
SPD503
n=121 participants at risk
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=57 participants at risk
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Asthma exacerbation
|
0.83%
1/121
|
0.00%
0/57
|
|
Injury, poisoning and procedural complications
Moderate loss of consciousness
|
0.83%
1/121
|
0.00%
0/57
|
Other adverse events
| Measure |
SPD503
n=121 participants at risk
Subjects received either 1, 2, or 3 mg once-daily of SPD503 (Guanfacine hydrochloride) for 6 weeks.
|
Placebo
n=57 participants at risk
|
|---|---|---|
|
Ear and labyrinth disorders
Ear pain
|
3.3%
4/121
|
0.00%
0/57
|
|
Gastrointestinal disorders
Abdominal pain
|
5.0%
6/121
|
1.8%
1/57
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
10/121
|
3.5%
2/57
|
|
Gastrointestinal disorders
Dry mouth
|
2.5%
3/121
|
0.00%
0/57
|
|
Gastrointestinal disorders
Vomiting
|
5.0%
6/121
|
1.8%
1/57
|
|
General disorders
Fatigue
|
5.0%
6/121
|
0.00%
0/57
|
|
General disorders
Non-cardiac chest pain
|
2.5%
3/121
|
0.00%
0/57
|
|
General disorders
Pyrexia
|
2.5%
3/121
|
0.00%
0/57
|
|
Nervous system disorders
Headache
|
24.8%
30/121
|
19.3%
11/57
|
|
Nervous system disorders
Sedation
|
7.4%
9/121
|
5.3%
3/57
|
|
Nervous system disorders
Somnolence
|
41.3%
50/121
|
22.8%
13/57
|
|
Psychiatric disorders
Insomnia
|
2.5%
3/121
|
1.8%
1/57
|
|
Psychiatric disorders
Irritability
|
5.0%
6/121
|
0.00%
0/57
|
|
Reproductive system and breast disorders
Dysmenorrhea
|
2.5%
3/121
|
0.00%
0/57
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER