Trial Outcomes & Findings for SPD503 (Guanfacine Hydrochloride) in ADHD Plus Oppositional Symptoms (NCT NCT00367835)
NCT ID: NCT00367835
Last Updated: 2021-06-14
Results Overview
The oppositional subscale of the CPRS-R:L contains 10 items designed to reflect criteria for oppositional defiance disorder (ODD). Each item is scored on a range from 0 (not true at all) to 3 (very much true) with total scores ranging from 0 to 30. Higher scores are reflective of more severe symptoms.
COMPLETED
PHASE3
217 participants
Baseline and up to 8 weeks
2021-06-14
Participant Flow
217 subjects were randomized (138 to SPD503 and 79 to placebo). However, only 214 subjects received at least one dose of study medication (136 for SPD503 and 78 for placebo). Therefore, 214 subjects constitute the safety population.
Participant milestones
| Measure |
SPD503
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
138
|
79
|
|
Overall Study
COMPLETED
|
109
|
48
|
|
Overall Study
NOT COMPLETED
|
29
|
31
|
Reasons for withdrawal
| Measure |
SPD503
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
|
|---|---|---|
|
Overall Study
Adverse Event
|
14
|
1
|
|
Overall Study
Protocol Violation
|
1
|
7
|
|
Overall Study
Withdrawal by Subject
|
7
|
6
|
|
Overall Study
Lost to Follow-up
|
1
|
4
|
|
Overall Study
Lack of Efficacy
|
3
|
12
|
|
Overall Study
Subject in juvenile detention center
|
1
|
0
|
|
Overall Study
refused blood collection
|
1
|
0
|
|
Overall Study
Did not respond to calls
|
1
|
0
|
|
Overall Study
History of lead poisoning
|
0
|
1
|
Baseline Characteristics
SPD503 (Guanfacine Hydrochloride) in ADHD Plus Oppositional Symptoms
Baseline characteristics by cohort
| Measure |
SPD503
n=138 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=79 Participants
|
Total
n=217 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
138 Participants
n=99 Participants
|
79 Participants
n=107 Participants
|
217 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
9.4 years
STANDARD_DEVIATION 1.73 • n=99 Participants
|
9.3 years
STANDARD_DEVIATION 2.04 • n=107 Participants
|
9.4 years
STANDARD_DEVIATION 1.84 • n=206 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
69 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
88 Participants
n=99 Participants
|
60 Participants
n=107 Participants
|
148 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
138 Participants
n=99 Participants
|
79 Participants
n=107 Participants
|
217 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline and up to 8 weeksPopulation: Full Analysis Set (FAS) defined as all randomized subjects who received at least one dose of any investigational product during this study and with a baseline and at least one post-baseline efficacy measurement.
The oppositional subscale of the CPRS-R:L contains 10 items designed to reflect criteria for oppositional defiance disorder (ODD). Each item is scored on a range from 0 (not true at all) to 3 (very much true) with total scores ranging from 0 to 30. Higher scores are reflective of more severe symptoms.
Outcome measures
| Measure |
SPD503
n=130 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=75 Participants
|
|---|---|---|
|
Change From Baseline in the Oppositional Subscale of the Conners' Parent Rating Scale-Revised Long Form (CPRS-R:L) Score at Up to 8 Weeks
|
-10.8 Units on a scale
Standard Deviation 7.23
|
-7.0 Units on a scale
Standard Deviation 7.63
|
SECONDARY outcome
Timeframe: Baseline and up to 8 weeksPopulation: FAS
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=130 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=75 Participants
|
|---|---|---|
|
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at Up to 8 Weeks
|
-23.8 Units on a scale
Standard Deviation 14.43
|
-11.4 Units on a scale
Standard Deviation 12.65
|
SECONDARY outcome
Timeframe: up to 8 weeksPopulation: FAS
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Outcome measures
| Measure |
SPD503
n=130 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=75 Participants
|
|---|---|---|
|
Assessment of Clinical Global Impression-Severity of Illness (CGI-S)
6 (Severely ill)
|
4 Participants
|
5 Participants
|
|
Assessment of Clinical Global Impression-Severity of Illness (CGI-S)
7 (Among the most extremely ill)
|
0 Participants
|
0 Participants
|
|
Assessment of Clinical Global Impression-Severity of Illness (CGI-S)
1 (Normal, not at all ill)
|
25 Participants
|
3 Participants
|
|
Assessment of Clinical Global Impression-Severity of Illness (CGI-S)
2 (Borderline mentally ill)
|
33 Participants
|
6 Participants
|
|
Assessment of Clinical Global Impression-Severity of Illness (CGI-S)
3 (Mildly ill)
|
29 Participants
|
15 Participants
|
|
Assessment of Clinical Global Impression-Severity of Illness (CGI-S)
4 (Moderately ill)
|
26 Participants
|
24 Participants
|
|
Assessment of Clinical Global Impression-Severity of Illness (CGI-S)
5 (Markedly ill)
|
13 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: up to 8 weeksPopulation: FAS
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=130 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=75 Participants
|
|---|---|---|
|
Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I)
|
93 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: Baseline and up to 8 weeksPopulation: FAS
Each item on the NYPRS-S is scored from a range of 0 (not at all) to 3 (very much) with total scores ranging from 0 to 120. Higher scores are reflective of increased disease severity.
Outcome measures
| Measure |
SPD503
n=130 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=75 Participants
|
|---|---|---|
|
Change From Baseline in the 40-Item Conduct Problem Scale of the New York Parent's Rating Scale-School-aged (NYPRS-S) Score at Up to 8 Weeks
|
-15.6 units on a scale
Standard Deviation 12.86
|
-10.3 units on a scale
Standard Deviation 13.25
|
SECONDARY outcome
Timeframe: Baseline and up to 8 weeksPopulation: FAS
The response to each of the 36 items on the PSI/SF is converted to a five-point scale from 1 (strongly agree) to 5 (strongly disagree) with total scores ranging from 36 to 180. A higher score is reflective of less stress for the parents.
Outcome measures
| Measure |
SPD503
n=109 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=57 Participants
|
|---|---|---|
|
Change From Baseline in the Parent Stress Index-Short Form (PSI/SF) Score at Up to 8 Weeks
|
17.3 Units on a scale
Standard Deviation 19.76
|
7.2 Units on a scale
Standard Deviation 18.29
|
SECONDARY outcome
Timeframe: up to 8 weeksPopulation: FAS
The Medication Satisfaction Survey (MSS) consists of 11 questions each being answered with one of six responses (strongly agree, agree, somewhat agree, somewhat disagree, disagree, strongly disagree). Overall satisfaction with their child taking the study medication, Question #11, with a response of "strongly agree" or "agree".
Outcome measures
| Measure |
SPD503
n=129 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=69 Participants
|
|---|---|---|
|
Number of Participants With Overall Satisfaction on the Medication Satisfaction Survey (MSS)
|
84 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: Baseline and up to 8 weeksPopulation: Safety population defined as all randomized subjects who received at least one dose of any investigational product during this study.
QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation.
Outcome measures
| Measure |
SPD503
n=107 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=58 Participants
|
|---|---|---|
|
Change From Baseline in Electrocardiogram Results (QTcF Interval) at Up to 8 Weeks
|
5.2 msec
Standard Deviation 15.74
|
2.1 msec
Standard Deviation 17.41
|
SECONDARY outcome
Timeframe: Baseline and up to 8 weeksPopulation: Safety population
Outcome measures
| Measure |
SPD503
n=130 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=75 Participants
|
|---|---|---|
|
Change From Baseline in Pulse Rate at Up to 8 Weeks
|
-4.3 beats/min
Standard Deviation 11.89
|
0.7 beats/min
Standard Deviation 11.44
|
SECONDARY outcome
Timeframe: Baseline and up to 8 weeksPopulation: Safety population
Outcome measures
| Measure |
SPD503
n=130 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=75 Participants
|
|---|---|---|
|
Change From Baseline in Systolic Blood Pressure at Up to 8 Weeks
|
-2.6 mmHg
Standard Deviation 10.27
|
0.7 mmHg
Standard Deviation 8.18
|
SECONDARY outcome
Timeframe: Baseline and up to 8 weeksPopulation: Safety population
Outcome measures
| Measure |
SPD503
n=130 Participants
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=75 Participants
|
|---|---|---|
|
Change From Baseline in Diastolic Blood Pressure at Up to 8 Weeks
|
-1.3 mmHg
Standard Deviation 8.48
|
0.9 mmHg
Standard Deviation 7.38
|
Adverse Events
SPD503
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
SPD503
n=136 participants at risk
Subjects will receive either 1, 2, 3, or 4 mg/day oral doses of SPD503 (Guanfacine hydrochloride)
|
Placebo
n=78 participants at risk
|
|---|---|---|
|
Nervous system disorders
Somnolence
|
50.7%
69/136
|
6.4%
5/78
|
|
Nervous system disorders
Headache
|
22.1%
30/136
|
17.9%
14/78
|
|
Nervous system disorders
Sedation
|
13.2%
18/136
|
1.3%
1/78
|
|
Nervous system disorders
Dizziness
|
5.1%
7/136
|
3.8%
3/78
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.8%
16/136
|
2.6%
2/78
|
|
Gastrointestinal disorders
Vomiting
|
7.4%
10/136
|
6.4%
5/78
|
|
Gastrointestinal disorders
Nausea
|
2.9%
4/136
|
6.4%
5/78
|
|
General disorders
Fatigue
|
11.0%
15/136
|
5.1%
4/78
|
|
Psychiatric disorders
Irritability
|
8.1%
11/136
|
2.6%
2/78
|
|
Psychiatric disorders
Affect lability
|
1.5%
2/136
|
5.1%
4/78
|
|
Investigations
Blood pressure diastolic decreased
|
5.9%
8/136
|
1.3%
1/78
|
|
Infections and infestations
Upper respiratory tract infection
|
4.4%
6/136
|
5.1%
4/78
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
3.7%
5/136
|
5.1%
4/78
|
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