Trial Outcomes & Findings for Safety and Tolerability of SPD503 and Psychostimulants in Children and Adolescents Aged 6-17 With Attention-Deficit/Hyperactivity Disorder (ADHD) (NCT NCT00151996)
NCT ID: NCT00151996
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.
COMPLETED
PHASE2
75 participants
Baseline and 6 weeks
2021-06-10
Participant Flow
Dose titration of SPD503 (Guanfacine HCl) for 3 weeks starting at 1 mg/day and increased in 1 mg weekly increments up to 4 mg/day (or to the highest tolerated dose); then dose maintenance for 3 weeks; then downward titration of SPD503 at 1 mg weekly decrements for 3 weeks while maintaining the subject's current psychostimulant dose and frequency.
Participant milestones
| Measure |
Methylphenidate + SPD503
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Methylphenidate was dosed according to the prescribing physician's instructions.
|
Amphetamine + SPD503
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Amphetamine was dosed according to the prescribing physician's instructions.
|
|---|---|---|
|
Overall Study
STARTED
|
42
|
33
|
|
Overall Study
COMPLETED
|
37
|
26
|
|
Overall Study
NOT COMPLETED
|
5
|
7
|
Reasons for withdrawal
| Measure |
Methylphenidate + SPD503
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Methylphenidate was dosed according to the prescribing physician's instructions.
|
Amphetamine + SPD503
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Amphetamine was dosed according to the prescribing physician's instructions.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Protocol Violation
|
1
|
2
|
|
Overall Study
Sponsor's decision
|
0
|
2
|
Baseline Characteristics
Safety and Tolerability of SPD503 and Psychostimulants in Children and Adolescents Aged 6-17 With Attention-Deficit/Hyperactivity Disorder (ADHD)
Baseline characteristics by cohort
| Measure |
Methylphenidate + SPD503
n=42 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Methylphenidate was dosed according to the prescribing physician's instructions.
|
Amphetamine + SPD503
n=33 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Amphetamine was dosed according to the prescribing physician's instructions.
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
42 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
11.1 years
STANDARD_DEVIATION 1.79 • n=5 Participants
|
11.6 years
STANDARD_DEVIATION 2.62 • n=7 Participants
|
11.4 years
STANDARD_DEVIATION 2.19 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
42 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 6 weeksPopulation: Full Analysis Set (FAS) defined as all subjects with a baseline and at least one post-baseline 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 |
Methylphenidate + SPD503
n=42 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Methylphenidate was dosed according to the prescribing physician's instructions.
|
Amphetamine + SPD503
n=32 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Amphetamine was dosed according to the prescribing physician's instructions.
|
|---|---|---|
|
Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at 6 Weeks
|
-17.8 Units on a Scale
Standard Deviation 10.2
|
-13.8 Units on a Scale
Standard Deviation 11.19
|
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 |
Methylphenidate + SPD503
n=42 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Methylphenidate was dosed according to the prescribing physician's instructions.
|
Amphetamine + SPD503
n=32 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Amphetamine was dosed according to the prescribing physician's instructions.
|
|---|---|---|
|
Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores
|
28 Participants
|
18 Participants
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksPopulation: FAS
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 |
Methylphenidate + SPD503
n=42 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Methylphenidate was dosed according to the prescribing physician's instructions.
|
Amphetamine + SPD503
n=32 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Amphetamine was dosed according to the prescribing physician's instructions.
|
|---|---|---|
|
Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Total Score at 6 Weeks
|
-22.18 Units on a Scale
Standard Deviation 15.47
|
-16.28 Units on a Scale
Standard Deviation 18.12
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: FAS
Parent Global Assessment (PGA) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The PGA is designed to capture parent's opinions of their child's disease (ADHD) severity and improvement. Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Outcome measures
| Measure |
Methylphenidate + SPD503
n=42 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Methylphenidate was dosed according to the prescribing physician's instructions.
|
Amphetamine + SPD503
n=32 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Amphetamine was dosed according to the prescribing physician's instructions.
|
|---|---|---|
|
Number of Participants With Improvement on Parent Global Assessment (PGA) Scores
|
32 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksPopulation: FAS
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 for each. Increases in scores represent improved well-being in subjects as assessed by their parents.
Outcome measures
| Measure |
Methylphenidate + SPD503
n=42 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Methylphenidate was dosed according to the prescribing physician's instructions.
|
Amphetamine + SPD503
n=32 Participants
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Amphetamine was dosed according to the prescribing physician's instructions.
|
|---|---|---|
|
Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Scores at 6 Weeks
Physical Summary Score
|
-0.38 Units on a scale
Standard Deviation 5.83
|
0.22 Units on a scale
Standard Deviation 11.94
|
|
Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Scores at 6 Weeks
Psychosocial Summary Score
|
8.98 Units on a scale
Standard Deviation 6.69
|
11.56 Units on a scale
Standard Deviation 10.00
|
Adverse Events
Methylphenidate + SPD503
Amphetamine + SPD503
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Methylphenidate + SPD503
n=42 participants at risk
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Methylphenidate was dosed according to the prescribing physician's instructions.
|
Amphetamine + SPD503
n=33 participants at risk
Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Amphetamine was dosed according to the prescribing physician's instructions.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
28.6%
12/42
|
36.4%
12/33
|
|
Gastrointestinal disorders
Constipation
|
2.4%
1/42
|
6.1%
2/33
|
|
Gastrointestinal disorders
Nausea
|
7.1%
3/42
|
0.00%
0/33
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
3/42
|
3.0%
1/33
|
|
General disorders
Fatigue
|
35.7%
15/42
|
33.3%
11/33
|
|
Infections and infestations
Upper respiratory tract infection
|
14.3%
6/42
|
6.1%
2/33
|
|
Metabolism and nutrition disorders
Anorexia
|
7.1%
3/42
|
9.1%
3/33
|
|
Metabolism and nutrition disorders
Appetite increased
|
0.00%
0/42
|
6.1%
2/33
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.4%
1/42
|
6.1%
2/33
|
|
Nervous system disorders
Dizziness
|
7.1%
3/42
|
0.00%
0/33
|
|
Nervous system disorders
Headache
|
28.6%
12/42
|
39.4%
13/33
|
|
Nervous system disorders
Sedation
|
9.5%
4/42
|
6.1%
2/33
|
|
Nervous system disorders
Somnolence
|
14.3%
6/42
|
24.2%
8/33
|
|
Psychiatric disorders
Anxiety
|
14.3%
6/42
|
15.2%
5/33
|
|
Psychiatric disorders
Depressed mood
|
2.4%
1/42
|
9.1%
3/33
|
|
Psychiatric disorders
Initial insomnia
|
4.8%
2/42
|
9.1%
3/33
|
|
Psychiatric disorders
Insomnia
|
16.7%
7/42
|
15.2%
5/33
|
|
Psychiatric disorders
Irritability
|
23.8%
10/42
|
42.4%
14/33
|
|
Psychiatric disorders
Social avoidant behavior
|
9.5%
4/42
|
3.0%
1/33
|
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