Trial Outcomes & Findings for Treatment of Impulsive Aggression (IA) in Adolescent With ADHD in Conjunction With Standard ADHD Treatment (NCT NCT03597503)
NCT ID: NCT03597503
Last Updated: 2024-04-24
Results Overview
The primary efficacy endpoint was percent change (PCHT) in the frequency (unweighted score) of IA behaviors per 7 days in the treatment (titration and maintenance) period relative to the baseline period calculated over the number of days with non-missing IA diary data. PCHT was then calculated as 100 x (T - B)/B, where T and B are IA behavior frequencies per 7 days during the treatment period (from Day 2 through Visit 7, inclusive) and baseline period (Day ≤1), respectively. The IA behavior frequency per 7 days is defined as (SUM/DAY) x 7, where SUM is the total of the IA behaviors reported in the subject IA diary, and DAY is the number of days with a non-missing IA score in the subject IA diary during the specified study period.
TERMINATED
PHASE3
41 participants
Daily measure from Visit 2 (Day -15) to Visit 7 (Day 36) for a total of 7 weeks
2024-04-24
Participant Flow
Participants underwent a 15-day baseline period (up to -Day 15), were randomized on Day 1 to receive either placebo or SPN-180, and then entered a 2- week titration phase followed by a 3-weeks maintenance phase, and then a 1-week taper phase.
Participant milestones
| Measure |
Placebo
Subjects treated with Placebo
|
Flexible Dose of SPN-810
Subjects treated with flexible dose of SPN-810 (36, 45 or 54 mg/day).
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
21
|
|
Overall Study
Treated
|
20
|
21
|
|
Overall Study
COMPLETED
|
18
|
17
|
|
Overall Study
NOT COMPLETED
|
2
|
4
|
Reasons for withdrawal
| Measure |
Placebo
Subjects treated with Placebo
|
Flexible Dose of SPN-810
Subjects treated with flexible dose of SPN-810 (36, 45 or 54 mg/day).
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
|
Overall Study
Protocol Violation
|
1
|
0
|
Baseline Characteristics
Treatment of Impulsive Aggression (IA) in Adolescent With ADHD in Conjunction With Standard ADHD Treatment
Baseline characteristics by cohort
| Measure |
Placebo
n=20 Participants
Subjects treated with Placebo
|
Flexible Dose of SPN-810
n=21 Participants
Subjects treated with flexible dose of SPN-810 (36, 45 or 54 mg/day).
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
13.1 years
STANDARD_DEVIATION 1.43 • n=5 Participants
|
13.2 years
STANDARD_DEVIATION 1.25 • n=7 Participants
|
13.1 years
STANDARD_DEVIATION 1.33 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Daily measure from Visit 2 (Day -15) to Visit 7 (Day 36) for a total of 7 weeksPopulation: Safety Population: safety population is defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment.
The primary efficacy endpoint was percent change (PCHT) in the frequency (unweighted score) of IA behaviors per 7 days in the treatment (titration and maintenance) period relative to the baseline period calculated over the number of days with non-missing IA diary data. PCHT was then calculated as 100 x (T - B)/B, where T and B are IA behavior frequencies per 7 days during the treatment period (from Day 2 through Visit 7, inclusive) and baseline period (Day ≤1), respectively. The IA behavior frequency per 7 days is defined as (SUM/DAY) x 7, where SUM is the total of the IA behaviors reported in the subject IA diary, and DAY is the number of days with a non-missing IA score in the subject IA diary during the specified study period.
Outcome measures
| Measure |
Placebo
n=20 Participants
Subjects treated with Placebo
|
Flexible Dose of SPN-810
n=21 Participants
Subjects treated with flexible dose of SPN-810 (36, 45 or 54 mg/day).
|
|---|---|---|
|
Effect of SPN-810 Treatment on the Frequency of Impulsive Aggression (IA) Behaviors Measured by the Impulsive Aggression Diary
|
-31.73 percent change in IA behaviors
Standard Deviation 25.510
|
-35.66 percent change in IA behaviors
Standard Deviation 77.422
|
SECONDARY outcome
Timeframe: From Baseline/Visit 3 (Day 1) to Visit 4 (Day 15), Visit 5 (Day 22), Visit 6 (Day 29), Visit 7 (Day 36)Population: Safety Population: safety population is defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment.
The Clinical Global Impression - Severity of Illness (CGI-S) is a single item clinician rating of clinician's assessment of the severity of IA behaviors. CGI-S was evaluated by the Investigator at each visit on a 7- point scale with 1=Normal, 2=Borderline ill, 3=Mildly ill, 4=Moderately ill, 5=Markedly ill, 6=Severely ill, and 7=Extremely ill. Data represent the change between Baseline (Visit 3/Day 1) and four time points: Visit 4 (Day 15); Visit 5 (Day 22), Visit 6 (Day 29) and Visit 7 (Day 36).
Outcome measures
| Measure |
Placebo
n=20 Participants
Subjects treated with Placebo
|
Flexible Dose of SPN-810
n=21 Participants
Subjects treated with flexible dose of SPN-810 (36, 45 or 54 mg/day).
|
|---|---|---|
|
Effect of SPN-810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S)
Visit 5
|
-0.7 score on a scale
Standard Deviation 0.73
|
-1.1 score on a scale
Standard Deviation 0.94
|
|
Effect of SPN-810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S)
Visit 4
|
-0.5 score on a scale
Standard Deviation 0.77
|
-0.6 score on a scale
Standard Deviation 0.69
|
|
Effect of SPN-810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S)
Visit 6
|
-1.1 score on a scale
Standard Deviation 0.96
|
-1.2 score on a scale
Standard Deviation 0.90
|
|
Effect of SPN-810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S)
Visit 7
|
-1.3 score on a scale
Standard Deviation 1.03
|
-1.4 score on a scale
Standard Deviation 1.00
|
SECONDARY outcome
Timeframe: From Baseline/Visit 3 (Day 1) to Visit 4 (Day 15), Visit 5 (Day 22), Visit 6 (Day 29) and Visit 7 (Day 36).Population: Safety Population: safety population is defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment.
R-MOAS scale gauges the severity of aggressive behavior: the frequency of the 16 behaviors is rated over the past week in 4 areas (VE, PH, PR, SE). For each open question in each area, the parent-rated the aggressive behaviors on a scale from 0 to 5 or more times. To each area corresponds a weighted category: Verbal Incidents (VE)=1, Incidents Toward Other (PH)=4, Incidents Involving Property (PR)=2 and Incidents Directed Toward Self (SE)=3. Therefore, the sum of each area yields a maximum weighted score of 20 (VE), 120 (PH), 60 (PR), and 90 (SE). The total score is the sum of the four area scores or 0-290; the higher the score, the more severe the aggressive behavior is. Data represent the total score change between the Baseline (Visit 3/Day 1) and four time points: Visit 4 (Day 15); Visit 5 (Day 22), Visit 6 (Day 29), and Visit 7 (Day 36).
Outcome measures
| Measure |
Placebo
n=20 Participants
Subjects treated with Placebo
|
Flexible Dose of SPN-810
n=21 Participants
Subjects treated with flexible dose of SPN-810 (36, 45 or 54 mg/day).
|
|---|---|---|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
VE Score Visit 4
|
-1.4 units on a scale
Standard Deviation 3.89
|
-5.9 units on a scale
Standard Deviation 4.32
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
PH Score Visit 4
|
-3.4 units on a scale
Standard Deviation 9.55
|
-4.8 units on a scale
Standard Deviation 12.62
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
PR Score Visit 4
|
-2.4 units on a scale
Standard Deviation 7.62
|
-6.6 units on a scale
Standard Deviation 6.57
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
SE Score Visit 4
|
-1.9 units on a scale
Standard Deviation 6.94
|
-4.6 units on a scale
Standard Deviation 10.46
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
Total Score Visit 4
|
-9.1 units on a scale
Standard Deviation 16.53
|
-21.9 units on a scale
Standard Deviation 19.22
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
VE Score Visit 5
|
-3.7 units on a scale
Standard Deviation 3.93
|
-7.3 units on a scale
Standard Deviation 5.03
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
PH Score Visit 5
|
-8.6 units on a scale
Standard Deviation 8.87
|
-12.4 units on a scale
Standard Deviation 12.34
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
PR Score Visit 5
|
-5.4 units on a scale
Standard Deviation 9.93
|
-9.1 units on a scale
Standard Deviation 8.41
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
SE Score Visit 5
|
-2.1 units on a scale
Standard Deviation 7.88
|
-6.0 units on a scale
Standard Deviation 9.09
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
Total Score Visit 5
|
-19.8 units on a scale
Standard Deviation 23.37
|
-34.9 units on a scale
Standard Deviation 25.76
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
VE Score Visit 6
|
-5.4 units on a scale
Standard Deviation 4.17
|
-6.6 units on a scale
Standard Deviation 5.12
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
PH Score Visit 6
|
-7.8 units on a scale
Standard Deviation 17.91
|
-12.2 units on a scale
Standard Deviation 11.00
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
PR Score Visit 6
|
-7.3 units on a scale
Standard Deviation 9.38
|
-7.6 units on a scale
Standard Deviation 6.13
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
SE Score Visit 6
|
-3.2 units on a scale
Standard Deviation 7.94
|
-3.5 units on a scale
Standard Deviation 6.30
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
Total Score Visit 6
|
-23.7 units on a scale
Standard Deviation 32.21
|
-30.0 units on a scale
Standard Deviation 15.41
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
VE Score Visit 7
|
-5.7 units on a scale
Standard Deviation 4.31
|
-7.5 units on a scale
Standard Deviation 4.99
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
PH Score Visit 7
|
-12.9 units on a scale
Standard Deviation 13.89
|
-11.3 units on a scale
Standard Deviation 9.51
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
PR Score Visit 7
|
-8.3 units on a scale
Standard Deviation 8.85
|
-9.6 units on a scale
Standard Deviation 6.60
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
SE Score Visit 7
|
-3.3 units on a scale
Standard Deviation 9.14
|
-3.9 units on a scale
Standard Deviation 6.85
|
|
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score
Total Score Visit 7
|
-30.2 units on a scale
Standard Deviation 29.99
|
-32.3 units on a scale
Standard Deviation 15.45
|
SECONDARY outcome
Timeframe: Visit 4 (Day 15), Visit 5 (Day 22), Visit 6 (Day 29) and Visit 7 (Day 36)Population: Safety Population: safety population is defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment.
The treatment effect on the R-MOAS was assessed to capture the severity of the aggressive behaviors. The remission rate was defined as percentage of subjects with a R-MOAS total score ≤ 10. Data represent the percentage of subjects at four time points during the treatment period: Visit 4 (Day 15); Visit 5 (Day 22), Visit 6 (Day 29) and Visit 7 (Day 36).
Outcome measures
| Measure |
Placebo
n=20 Participants
Subjects treated with Placebo
|
Flexible Dose of SPN-810
n=21 Participants
Subjects treated with flexible dose of SPN-810 (36, 45 or 54 mg/day).
|
|---|---|---|
|
Effect of SPN-810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Remission Rate
Visit 4
|
10.5 percentage of participants
|
26.3 percentage of participants
|
|
Effect of SPN-810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Remission Rate
Visit 5
|
21.1 percentage of participants
|
33.3 percentage of participants
|
|
Effect of SPN-810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Remission Rate
Visit 6
|
27.8 percentage of participants
|
41.2 percentage of participants
|
|
Effect of SPN-810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Remission Rate
Visit 7
|
38.9 percentage of participants
|
58.8 percentage of participants
|
Adverse Events
Placebo
Flexible Dose of SPN-810
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=20 participants at risk
Subjects treated with Placebo
|
Flexible Dose of SPN-810
n=21 participants at risk
Subjects treated with flexible dose of SPN-810 (36, 45 or 54 mg/day)
|
|---|---|---|
|
Nervous system disorders
Headache
|
10.0%
2/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
9.5%
2/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Nervous system disorders
Somnolence
|
10.0%
2/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
0.00%
0/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Nervous system disorders
Dystonia
|
5.0%
1/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
0.00%
0/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Nervous system disorders
Lethargy
|
5.0%
1/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
0.00%
0/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Nervous system disorders
Parkinsonism
|
5.0%
1/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
0.00%
0/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Gastrointestinal disorders
Nausea
|
10.0%
2/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
4.8%
1/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Infections and infestations
Upper respiratory tract infection
|
5.0%
1/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
4.8%
1/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Infections and infestations
Conjunctivitis bacterial
|
5.0%
1/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
0.00%
0/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Metabolism and nutrition disorders
Increased appetite
|
10.0%
2/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
4.8%
1/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.0%
1/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
0.00%
0/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Injury, poisoning and procedural complications
Hand fracture
|
5.0%
1/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
0.00%
0/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.0%
1/20 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
0.00%
0/21 • Baseline/Visit 3 (Day 1) to Visit 8 (Day 46)-End of Study, a total of 46 days
Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug and had at least one post-baseline safety assessment
|
Additional Information
Gianpiera Ceresoli-Borroni/ Director Clinical Development
Supernus
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place