Trial Outcomes & Findings for Safety and Efficacy of SPD503 in Treating ADHD in Children and Adolescents Aged 6-17 (NCT NCT00150618)
NCT ID: NCT00150618
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
324 participants
Primary outcome timeframe
Baseline and 6 weeks
Results posted on
2021-06-10
Participant Flow
Although 324 subjects were randomized, 2 never received drug and therefore were not included in the Baseline Characteristics. Subjects received either 1, 2, 3, or 4 mg of SPD503 (Guanfacine hydrochloride) or placebo once daily.
Participant milestones
| Measure |
SPD503 (1 mg)
Guanfacine HCl once daily
|
SPD503 (2 mg)
Guanfacine HCl once daily
|
SPD503 (3 mg)
Guanfacine HCl once daily
|
SPD503 (4 mg)
Guanfacine HCl once daily
|
Placebo
once daily
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
62
|
65
|
65
|
66
|
66
|
|
Overall Study
COMPLETED
|
45
|
47
|
38
|
40
|
41
|
|
Overall Study
NOT COMPLETED
|
17
|
18
|
27
|
26
|
25
|
Reasons for withdrawal
| Measure |
SPD503 (1 mg)
Guanfacine HCl once daily
|
SPD503 (2 mg)
Guanfacine HCl once daily
|
SPD503 (3 mg)
Guanfacine HCl once daily
|
SPD503 (4 mg)
Guanfacine HCl once daily
|
Placebo
once daily
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
2
|
6
|
9
|
5
|
|
Overall Study
Withdrawal by Subject
|
6
|
8
|
8
|
4
|
5
|
|
Overall Study
Lost to Follow-up
|
4
|
1
|
5
|
8
|
4
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
4
|
7
|
4
|
6
|
|
Overall Study
No study meds
|
0
|
0
|
0
|
0
|
2
|
|
Overall Study
Physician Decision
|
0
|
2
|
0
|
0
|
1
|
|
Overall Study
Lack of compliance
|
2
|
1
|
1
|
0
|
1
|
|
Overall Study
Abnormal ECG
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Sponsor's decision
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Safety and Efficacy of SPD503 in Treating ADHD in Children and Adolescents Aged 6-17
Baseline characteristics by cohort
| Measure |
SPD503 (1 mg)
n=61 Participants
Guanfacine HCl once daily
|
SPD503 (2 mg)
n=65 Participants
Guanfacine HCl once daily
|
SPD503 (3 mg)
n=65 Participants
Guanfacine HCl once daily
|
SPD503 (4 mg)
n=65 Participants
Guanfacine HCl once daily
|
Placebo
n=66 Participants
once daily
|
Total
n=322 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
61 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
66 Participants
n=21 Participants
|
322 Participants
n=8 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
|
0 Participants
n=8 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
|
0 Participants
n=8 Participants
|
|
Age, Continuous
|
9.3 years
STANDARD_DEVIATION 2.14 • n=5 Participants
|
10.6 years
STANDARD_DEVIATION 2.81 • n=7 Participants
|
11.1 years
STANDARD_DEVIATION 2.96 • n=5 Participants
|
10.5 years
STANDARD_DEVIATION 2.53 • n=4 Participants
|
10.8 years
STANDARD_DEVIATION 2.89 • n=21 Participants
|
10.5 years
STANDARD_DEVIATION 2.74 • n=8 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
89 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
53 Participants
n=4 Participants
|
45 Participants
n=21 Participants
|
233 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
61 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
66 Participants
n=21 Participants
|
322 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline and 6 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 (1 mg)
n=57 Participants
Guanfacine HCl once daily
|
SPD503 (2 mg)
n=63 Participants
Guanfacine HCl once daily
|
SPD503 (3 mg)
n=60 Participants
Guanfacine HCl once daily
|
SPD503 (4 mg)
n=63 Participants
Guanfacine HCl once daily
|
Placebo
n=63 Participants
once daily
|
|---|---|---|---|---|---|
|
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at 6 Weeks
|
-19.44 Units on a Scale
Standard Error 1.69
|
-18.09 Units on a Scale
Standard Error 1.60
|
-20.00 Units on a Scale
Standard Error 1.64
|
-20.57 Units on a Scale
Standard Error 1.60
|
-12.69 Units on a Scale
Standard Error 1.60
|
SECONDARY outcome
Timeframe: Baseline and 6 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) to 3 (very much true) 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 (1 mg)
n=52 Participants
Guanfacine HCl once daily
|
SPD503 (2 mg)
n=55 Participants
Guanfacine HCl once daily
|
SPD503 (3 mg)
n=47 Participants
Guanfacine HCl once daily
|
SPD503 (4 mg)
n=53 Participants
Guanfacine HCl once daily
|
Placebo
n=53 Participants
once daily
|
|---|---|---|---|---|---|
|
Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at 6 Weeks
|
-19.50 Units on a Scale
Standard Error 2.36
|
-14.96 Units on a Scale
Standard Error 2.29
|
-17.94 Units on a Scale
Standard Error 2.48
|
-15.93 Units on a Scale
Standard Error 2.34
|
-8.41 Units on a Scale
Standard Error 2.34
|
SECONDARY outcome
Timeframe: 6 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 (1 mg)
n=57 Participants
Guanfacine HCl once daily
|
SPD503 (2 mg)
n=63 Participants
Guanfacine HCl once daily
|
SPD503 (3 mg)
n=60 Participants
Guanfacine HCl once daily
|
SPD503 (4 mg)
n=63 Participants
Guanfacine HCl once daily
|
Placebo
n=63 Participants
once daily
|
|---|---|---|---|---|---|
|
Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I)
|
31 Participants
|
27 Participants
|
33 Participants
|
35 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: 6 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 (1 mg)
n=53 Participants
Guanfacine HCl once daily
|
SPD503 (2 mg)
n=55 Participants
Guanfacine HCl once daily
|
SPD503 (3 mg)
n=47 Participants
Guanfacine HCl once daily
|
SPD503 (4 mg)
n=53 Participants
Guanfacine HCl once daily
|
Placebo
n=53 Participants
once daily
|
|---|---|---|---|---|---|
|
Number of Participants With Improvement in Parent Global Assessment (PGA)
|
27 Participants
|
20 Participants
|
29 Participants
|
30 Participants
|
16 Participants
|
SECONDARY outcome
Timeframe: Baseline and 6 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 scoring ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents.
Outcome measures
| Measure |
SPD503 (1 mg)
n=48 Participants
Guanfacine HCl once daily
|
SPD503 (2 mg)
n=45 Participants
Guanfacine HCl once daily
|
SPD503 (3 mg)
n=37 Participants
Guanfacine HCl once daily
|
SPD503 (4 mg)
n=40 Participants
Guanfacine HCl once daily
|
Placebo
n=42 Participants
once daily
|
|---|---|---|---|---|---|
|
Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks
Physical
|
0.32 units on a scale
Standard Error 0.87
|
0.35 units on a scale
Standard Error 0.89
|
-0.91 units on a scale
Standard Error 0.99
|
-2.44 units on a scale
Standard Error 0.95
|
-0.01 units on a scale
Standard Error 0.92
|
|
Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks
Psychosocial
|
10.61 units on a scale
Standard Error 1.41
|
7.47 units on a scale
Standard Error 1.44
|
9.07 units on a scale
Standard Error 1.61
|
9.43 units on a scale
Standard Error 1.53
|
6.34 units on a scale
Standard Error 1.49
|
Adverse Events
SPD503 (1 mg)
Serious events: 0 serious events
Other events: 49 other events
Deaths: 0 deaths
SPD503 (2 mg)
Serious events: 0 serious events
Other events: 40 other events
Deaths: 0 deaths
SPD503 (3 mg)
Serious events: 1 serious events
Other events: 45 other events
Deaths: 0 deaths
SPD503 (4 mg)
Serious events: 0 serious events
Other events: 55 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SPD503 (1 mg)
n=61 participants at risk
Guanfacine HCl once daily
|
SPD503 (2 mg)
n=65 participants at risk
Guanfacine HCl once daily
|
SPD503 (3 mg)
n=65 participants at risk
Guanfacine HCl once daily
|
SPD503 (4 mg)
n=65 participants at risk
Guanfacine HCl once daily
|
Placebo
n=66 participants at risk
once daily
|
|---|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/61
|
0.00%
0/65
|
1.5%
1/65 • Number of events 1
|
0.00%
0/65
|
0.00%
0/66
|
|
Nervous system disorders
Convulsion
|
0.00%
0/61
|
0.00%
0/65
|
1.5%
1/65 • Number of events 1
|
0.00%
0/65
|
0.00%
0/66
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/61
|
0.00%
0/65
|
0.00%
0/65
|
0.00%
0/65
|
1.5%
1/66 • Number of events 1
|
Other adverse events
| Measure |
SPD503 (1 mg)
n=61 participants at risk
Guanfacine HCl once daily
|
SPD503 (2 mg)
n=65 participants at risk
Guanfacine HCl once daily
|
SPD503 (3 mg)
n=65 participants at risk
Guanfacine HCl once daily
|
SPD503 (4 mg)
n=65 participants at risk
Guanfacine HCl once daily
|
Placebo
n=66 participants at risk
once daily
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Upper abdominal pain
|
8.2%
5/61
|
3.1%
2/65
|
1.5%
1/65
|
12.3%
8/65
|
9.1%
6/66
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/61
|
0.00%
0/65
|
1.5%
1/65
|
7.7%
5/65
|
1.5%
1/66
|
|
Gastrointestinal disorders
Nausea
|
6.6%
4/61
|
3.1%
2/65
|
4.6%
3/65
|
6.2%
4/65
|
1.5%
1/66
|
|
Gastrointestinal disorders
Vomiting
|
1.6%
1/61
|
3.1%
2/65
|
4.6%
3/65
|
1.5%
1/65
|
6.1%
4/66
|
|
General disorders
Fatigue
|
9.8%
6/61
|
4.6%
3/65
|
10.8%
7/65
|
12.3%
8/65
|
3.0%
2/66
|
|
General disorders
Lethargy
|
1.6%
1/61
|
0.00%
0/65
|
7.7%
5/65
|
4.6%
3/65
|
1.5%
1/66
|
|
Nervous system disorders
Dizziness
|
4.9%
3/61
|
0.00%
0/65
|
9.2%
6/65
|
9.2%
6/65
|
6.1%
4/66
|
|
Nervous system disorders
Headache
|
26.2%
16/61
|
24.6%
16/65
|
7.7%
5/65
|
24.6%
16/65
|
10.6%
7/66
|
|
Nervous system disorders
Sedation
|
1.6%
1/61
|
9.2%
6/65
|
4.6%
3/65
|
7.7%
5/65
|
4.5%
3/66
|
|
Nervous system disorders
Somnolence
|
26.2%
16/61
|
16.9%
11/65
|
23.1%
15/65
|
41.5%
27/65
|
12.1%
8/66
|
|
Psychiatric disorders
Irritability
|
6.6%
4/61
|
6.2%
4/65
|
3.1%
2/65
|
6.2%
4/65
|
4.5%
3/66
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.6%
4/61
|
1.5%
1/65
|
3.1%
2/65
|
1.5%
1/65
|
0.00%
0/66
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
3.3%
2/61
|
1.5%
1/65
|
1.5%
1/65
|
1.5%
1/65
|
6.1%
4/66
|
|
Vascular disorders
Hypotension
|
3.3%
2/61
|
1.5%
1/65
|
6.2%
4/65
|
4.6%
3/65
|
1.5%
1/66
|
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