Trial Outcomes & Findings for Safety and Efficacy of SPD503 in Treating Attention-Deficit/Hyperactivity Disorder (ADHD) in Children Aged 6-17 (NCT NCT00152009)
NCT ID: NCT00152009
Last Updated: 2021-06-10
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
345 participants
Primary outcome timeframe
Baseline and up to 5 weeks
Results posted on
2021-06-10
Participant Flow
Subjects were randomized to receive either 2, 3, or 4 mg SPD503 (Guanfacine hydrochloride) or placebo once-daily.
Participant milestones
| Measure |
SPD503 2mg
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
Subjects were randomized to receive Placebo once-daily.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
87
|
86
|
86
|
86
|
|
Overall Study
COMPLETED
|
58
|
55
|
49
|
53
|
|
Overall Study
NOT COMPLETED
|
29
|
31
|
37
|
33
|
Reasons for withdrawal
| Measure |
SPD503 2mg
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
Subjects were randomized to receive Placebo once-daily.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
9
|
13
|
20
|
1
|
|
Overall Study
Protocol Violation
|
3
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
4
|
9
|
|
Overall Study
Lost to Follow-up
|
2
|
4
|
3
|
3
|
|
Overall Study
Lack of Efficacy
|
8
|
6
|
7
|
15
|
|
Overall Study
ECG abnormalities
|
2
|
2
|
2
|
1
|
|
Overall Study
Sponsor's decision
|
3
|
3
|
1
|
3
|
Baseline Characteristics
Safety and Efficacy of SPD503 in Treating Attention-Deficit/Hyperactivity Disorder (ADHD) in Children Aged 6-17
Baseline characteristics by cohort
| Measure |
SPD503 2mg
n=87 Participants
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
n=86 Participants
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
n=86 Participants
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
n=86 Participants
Subjects were randomized to receive Placebo once-daily.
|
Total
n=345 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
87 Participants
n=5 Participants
|
86 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
86 Participants
n=4 Participants
|
345 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Continuous
|
10.6 years
STANDARD_DEVIATION 2.35 • n=5 Participants
|
10.8 years
STANDARD_DEVIATION 2.76 • n=7 Participants
|
10.1 years
STANDARD_DEVIATION 2.86 • n=5 Participants
|
10.6 years
STANDARD_DEVIATION 2.70 • n=4 Participants
|
10.5 years
STANDARD_DEVIATION 2.68 • n=21 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
88 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
67 Participants
n=5 Participants
|
69 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
64 Participants
n=4 Participants
|
257 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
87 Participants
n=5 Participants
|
86 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
86 Participants
n=4 Participants
|
345 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and up to 5 weeksPopulation: Intent to treat (ITT) defined as all subjects who were randomized to treatment and had the baseline and at least one post-randomization primary efficacy measurement.
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 2mg
n=84 Participants
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
n=82 Participants
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
n=81 Participants
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
n=78 Participants
Subjects were randomized to receive Placebo once-daily.
|
|---|---|---|---|---|
|
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at Up to 5 Weeks
|
-15.93 Units on a Scale
Standard Error 1.37
|
-16.03 Units on a Scale
Standard Error 1.38
|
-18.51 Units on a Scale
Standard Error 1.39
|
-8.51 Units on a Scale
Standard Error 1.42
|
SECONDARY outcome
Timeframe: Baseline and up to 5 weeksPopulation: ITT
The Conner's Parent rating Scale-revised short version (CPRS-R) consists of 27 questions graded on a scale from 0 (not true at all) reflecting no symptoms to 3 (very much true) reflecting severe symptoms with a total score ranging from 0 to 81. Higher scores are indicative of increased ADHD. This scale allows parents to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior.
Outcome measures
| Measure |
SPD503 2mg
n=66 Participants
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
n=61 Participants
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
n=58 Participants
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
n=65 Participants
Subjects were randomized to receive Placebo once-daily.
|
|---|---|---|---|---|
|
Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at Up to 5 Weeks
|
-15.59 Units on a Scale
Standard Error 1.86
|
-15.43 Units on a Scale
Standard Error 1.95
|
-21.49 Units on a Scale
Standard Error 2.00
|
-8.66 Units on a Scale
Standard Error 1.87
|
SECONDARY outcome
Timeframe: Baseline and up to 5 weeksPopulation: ITT
The Conner's Teacher Rating Scale-revised short version (CTRS-R) consists of 28 questions graded on a scale from 0 (not true at all) reflecting no symptoms to 3 (very much true) reflecting severe symptoms with a total score ranging from 0 to 84. Higher scores are indicative of increased ADHD. This scale allows teachers to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior.
Outcome measures
| Measure |
SPD503 2mg
n=63 Participants
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
n=56 Participants
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
n=56 Participants
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
n=62 Participants
Subjects were randomized to receive Placebo once-daily.
|
|---|---|---|---|---|
|
Change From Baseline in Conner's Teacher Rating Scale-revised Short Version (CTRS-R) Score at Up to 5 Weeks
|
-13.02 Units on a Scale
Standard Error 1.69
|
-14.88 Units on a Scale
Standard Error 1.79
|
-15.26 Units on a Scale
Standard Error 1.80
|
-2.17 Units on a Scale
Standard Error 1.70
|
SECONDARY outcome
Timeframe: up to 5 weeksPopulation: ITT
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 2mg
n=84 Participants
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
n=82 Participants
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
n=81 Participants
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
n=78 Participants
Subjects were randomized to receive Placebo once-daily.
|
|---|---|---|---|---|
|
Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I)
|
47 Participants
|
41 Participants
|
45 Participants
|
20 Participants
|
SECONDARY outcome
Timeframe: up to 5 weeksPopulation: ITT
Parent Global Assessment (PGA) 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 2mg
n=66 Participants
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
n=61 Participants
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
n=59 Participants
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
n=65 Participants
Subjects were randomized to receive Placebo once-daily.
|
|---|---|---|---|---|
|
Number of Participants With Improvement in Parent Global Assessment (PGA)
|
41 Participants
|
31 Participants
|
39 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: Baseline and 5 weeksPopulation: ITT
The Child Health Questionnaire-Parent Form (CHQ-PF50) was developed to measure the physical and psychosocial well-being of children aged 5 years of age and older. Total score ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents.
Outcome measures
| Measure |
SPD503 2mg
n=61 Participants
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
n=61 Participants
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
n=52 Participants
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
n=58 Participants
Subjects were randomized to receive Placebo once-daily.
|
|---|---|---|---|---|
|
Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks
Psychosocial
|
9.03 Units on a scale
Standard Error 1.22
|
9.01 Units on a scale
Standard Error 1.20
|
10.64 Units on a scale
Standard Error 1.32
|
5.72 Units on a scale
Standard Error 1.23
|
|
Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks
Physical
|
0.24 Units on a scale
Standard Error 0.84
|
-1.82 Units on a scale
Standard Error 0.84
|
-2.13 Units on a scale
Standard Error 0.92
|
-0.18 Units on a scale
Standard Error 0.86
|
Adverse Events
SPD503 2mg
Serious events: 0 serious events
Other events: 67 other events
Deaths: 0 deaths
SPD503 3mg
Serious events: 1 serious events
Other events: 76 other events
Deaths: 0 deaths
SPD503 4mg
Serious events: 1 serious events
Other events: 75 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 55 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SPD503 2mg
n=87 participants at risk
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
n=86 participants at risk
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
n=86 participants at risk
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
n=86 participants at risk
Subjects were randomized to receive Placebo once-daily.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
pneumothorax
|
0.00%
0/87
|
1.2%
1/86
|
0.00%
0/86
|
0.00%
0/86
|
|
Respiratory, thoracic and mediastinal disorders
Asthma aggravated
|
0.00%
0/87
|
0.00%
0/86
|
1.2%
1/86
|
0.00%
0/86
|
Other adverse events
| Measure |
SPD503 2mg
n=87 participants at risk
Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 3mg
n=86 participants at risk
Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
SPD503 4mg
n=86 participants at risk
Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily.
|
Placebo
n=86 participants at risk
Subjects were randomized to receive Placebo once-daily.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.3%
9/87
|
16.3%
14/86
|
16.3%
14/86
|
5.8%
5/86
|
|
Gastrointestinal disorders
Dry mouth
|
2.3%
2/87
|
9.3%
8/86
|
5.8%
5/86
|
1.2%
1/86
|
|
Gastrointestinal disorders
Nausea
|
6.9%
6/87
|
5.8%
5/86
|
5.8%
5/86
|
2.3%
2/86
|
|
General disorders
Fatigue
|
18.4%
16/87
|
20.9%
18/86
|
15.1%
13/86
|
3.5%
3/86
|
|
General disorders
Lethargy
|
5.7%
5/87
|
8.1%
7/86
|
9.3%
8/86
|
3.5%
3/86
|
|
General disorders
Pyrexia
|
2.3%
2/87
|
0.00%
0/86
|
7.0%
6/86
|
3.5%
3/86
|
|
Infections and infestations
Upper respiratory tract infection
|
3.4%
3/87
|
5.8%
5/86
|
2.3%
2/86
|
3.5%
3/86
|
|
Metabolism and nutrition disorders
Appetite decreased
|
5.7%
5/87
|
9.3%
8/86
|
5.8%
5/86
|
2.3%
2/86
|
|
Nervous system disorders
Dizziness
|
4.6%
4/87
|
5.8%
5/86
|
10.5%
9/86
|
2.3%
2/86
|
|
Nervous system disorders
Headache
|
26.4%
23/87
|
22.1%
19/86
|
30.2%
26/86
|
24.4%
21/86
|
|
Nervous system disorders
Sedation
|
9.2%
8/87
|
12.8%
11/86
|
16.3%
14/86
|
3.5%
3/86
|
|
Nervous system disorders
Somnolence
|
24.1%
21/87
|
33.7%
29/86
|
38.4%
33/86
|
3.5%
3/86
|
|
Psychiatric disorders
Insomnia
|
5.7%
5/87
|
8.1%
7/86
|
5.8%
5/86
|
4.7%
4/86
|
|
Psychiatric disorders
Irritability
|
10.3%
9/87
|
2.3%
2/86
|
5.8%
5/86
|
3.5%
3/86
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.4%
3/87
|
5.8%
5/86
|
8.1%
7/86
|
5.8%
5/86
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.3%
2/87
|
2.3%
2/86
|
5.8%
5/86
|
3.5%
3/86
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
4.6%
4/87
|
4.7%
4/86
|
3.5%
3/86
|
5.8%
5/86
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
2.3%
2/87
|
4.7%
4/86
|
5.8%
5/86
|
4.7%
4/86
|
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