Trial Outcomes & Findings for Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 4) (NCT NCT02691182)

Last Updated: 2024-05-16

Results Overview

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. The data represent the total score change from baseline at each visit for the duration of the study, a total of 60 months. The baseline score represents the total score at the last visit of each double-blind study.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

491 participants

Primary outcome timeframe

17-time points: Months 3 (V5), 6 (V6), 9 (V7), 12 (V8), 15 (V9), 18 (V10), 21 (V11), 24 (V12), 27 (V13), 30 (V14), 33 (V15), 36 (V16), 39 (V17), 42 (V18), 45 (V19), 48 (V20) and month 60 (Visit 24).

Results posted on

2024-05-16

Participant Flow

Participant milestones

Participant milestones
Measure	<18 mg SPN-810 Subjects treated with 6, 12 or 15 mg/day SPN-810.	18 mg to < 24 mg SPN-810 Subjects treated with 18 mg/day, or 21 mg/day SPN-810	24 mg to < 36 mg SPN-810 Subjects treated with 24, 27 or 30 mg/day SPN-810	36 mg to ≤54 mg SPN-810 Subjects treated with 36, 42, 45, 48 or 54 mg/day SPN-810
Overall Study STARTED	38	159	131	163
Overall Study COMPLETED	0	1	2	1
Overall Study NOT COMPLETED	38	158	129	162

Reasons for withdrawal

Reasons for withdrawal
Measure	<18 mg SPN-810 Subjects treated with 6, 12 or 15 mg/day SPN-810.	18 mg to < 24 mg SPN-810 Subjects treated with 18 mg/day, or 21 mg/day SPN-810	24 mg to < 36 mg SPN-810 Subjects treated with 24, 27 or 30 mg/day SPN-810	36 mg to ≤54 mg SPN-810 Subjects treated with 36, 42, 45, 48 or 54 mg/day SPN-810
Overall Study Withdrawal by Subject	4	7	6	8
Overall Study Withdrawal by Parent/Guardian	9	47	33	38
Overall Study Lost to Follow-up	8	33	19	22
Overall Study Adverse Event	3	10	10	11
Overall Study Physician Decision	3	7	14	8
Overall Study Lack of Efficacy	0	0	0	4
Overall Study Protocol Violation	2	6	6	8
Overall Study Sponsor terminated study, SM non-compliance, Site closure, Subjects relocated or hospitalized.	9	43	40	58
Overall Study Missing	0	5	1	5

Baseline Characteristics

Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 4)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	<18 mg SPN-810 n=38 Participants Subjects treated with 6,12 or 15 mg/day SPN-810	18 mg to <24 mg SPN-810 n=159 Participants Subjects treated with 18 mg/day or 21 mg/day SPN-810	24 mg to <36 mg SPN-810 n=131 Participants Subjects treated with 24, 27 or 30 mg/day SPN-810	36 mg to ≤54 mg SPN-810 n=163 Participants Subjects treated with 36, 42, 45, 48 or 54 mg/day SPN-810	Total n=491 Participants Total of all reporting groups
Age, Continuous	8.6 years STANDARD_DEVIATION 1.78 • n=99 Participants	9.3 years STANDARD_DEVIATION 1.92 • n=107 Participants	9.2 years STANDARD_DEVIATION 1.91 • n=206 Participants	9.9 years STANDARD_DEVIATION 2.14 • n=7 Participants	9.4 years STANDARD_DEVIATION 2.02 • n=31 Participants
Age, Customized 6-12	38 participants n=99 Participants	154 participants n=107 Participants	128 participants n=206 Participants	147 participants n=7 Participants	467 participants n=31 Participants
Age, Customized 12-17	0 participants n=99 Participants	5 participants n=107 Participants	3 participants n=206 Participants	16 participants n=7 Participants	24 participants n=31 Participants
Sex: Female, Male Female	9 Participants n=99 Participants	34 Participants n=107 Participants	29 Participants n=206 Participants	32 Participants n=7 Participants	104 Participants n=31 Participants
Sex: Female, Male Male	29 Participants n=99 Participants	125 Participants n=107 Participants	102 Participants n=206 Participants	131 Participants n=7 Participants	387 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=99 Participants	26 Participants n=107 Participants	26 Participants n=206 Participants	29 Participants n=7 Participants	87 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=99 Participants	131 Participants n=107 Participants	104 Participants n=206 Participants	133 Participants n=7 Participants	400 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants	4 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	3 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants	5 Participants n=31 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	1 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants
Race (NIH/OMB) Black or African American	11 Participants n=99 Participants	57 Participants n=107 Participants	26 Participants n=206 Participants	41 Participants n=7 Participants	135 Participants n=31 Participants
Race (NIH/OMB) White	26 Participants n=99 Participants	88 Participants n=107 Participants	101 Participants n=206 Participants	110 Participants n=7 Participants	325 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	10 Participants n=107 Participants	4 Participants n=206 Participants	9 Participants n=7 Participants	24 Participants n=31 Participants

PRIMARY outcome

Timeframe: 17-time points: Months 3 (V5), 6 (V6), 9 (V7), 12 (V8), 15 (V9), 18 (V10), 21 (V11), 24 (V12), 27 (V13), 30 (V14), 33 (V15), 36 (V16), 39 (V17), 42 (V18), 45 (V19), 48 (V20) and month 60 (Visit 24).

Population: Safety Population: Safety population is defined as all subjects who received at least 1 dose of study drug during the study.

Outcome measures

Outcome measures
Measure	<18 mg SPN-810 n=38 Participants Subjects treated with 6, 12 or 15 mg/day SPN-810	18 mg to < 24 mg SPN-810 n=159 Participants Subjects treated with 18 mg/day or 21 mg/day SPN-810	24 mg to < 36 mg SPN-810 n=131 Participants Subjects treated with 24, 27 or 30 mg/day SPN-810	36 mg to ≤54 mg SPN-810 n=163 Participants Subjects treated with 36, 42, 45, 48 or 54 mg/day SPN-810
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 39	0.0 score on a scale	-7.7 score on a scale Standard Deviation 5.71	4.5 score on a scale Standard Deviation 6.36	-3.9 score on a scale Standard Deviation 9.06
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 39	-12.0 score on a scale	-41.6 score on a scale Standard Deviation 13.18	-9.0 score on a scale Standard Deviation 31.11	-51.6 score on a scale Standard Deviation 27.62
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 42	—	-7.0 score on a scale	-9.0 score on a scale Standard Deviation 7.07	-8.9 score on a scale Standard Deviation 5.37
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 42	—	-18.0 score on a scale	-7.0 score on a scale Standard Deviation 7.07	-15.1 score on a scale Standard Deviation 13.85
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 15	-37.8 score on a scale Standard Deviation 26.08	-50.7 score on a scale Standard Deviation 43.31	-47.6 score on a scale Standard Deviation 26.68	-42.9 score on a scale Standard Deviation 33.47
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 36	0.0 score on a scale	-8.8 score on a scale Standard Deviation 9.78	-4.0 score on a scale Standard Deviation 6.24	-5.5 score on a scale Standard Deviation 6.91
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 42	—	-3.0 score on a scale	-3.0 score on a scale Standard Deviation 4.24	-5.6 score on a scale Standard Deviation 8.20
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 42	—	-40.0 score on a scale	-33.0 score on a scale Standard Deviation 15.56	-57.0 score on a scale Standard Deviation 32.17
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 45	—	-7.0 score on a scale	—	-8.3 score on a scale Standard Deviation 2.08
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 45	—	-8.0 score on a scale	—	-24.0 score on a scale Standard Deviation 16.00
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 45	—	-14.0 score on a scale	—	-14.7 score on a scale Standard Deviation 7.57
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 45	—	-18.0 score on a scale	—	-2.0 score on a scale Standard Deviation 9.17
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 45	—	-47.0 score on a scale	—	-49.0 score on a scale Standard Deviation 22.07
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 48	—	—	—	-9.0 score on a scale
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 48	—	—	—	-28.0 score on a scale
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 48	—	—	—	-6.0 score on a scale
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 48	—	—	—	-12.0 score on a scale
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 48	—	—	—	-55.0 score on a scale
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 60	—	—	-10.0 score on a scale	-12.0 score on a scale
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 60	—	—	12.0 score on a scale	-12.0 score on a scale
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 60	—	—	-12.0 score on a scale	-12.0 score on a scale
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 60	—	—	3.0 score on a scale	-6.0 score on a scale
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 60	—	—	-7.0 score on a scale	-42.0 score on a scale
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 18	-5.8 score on a scale Standard Deviation 7.03	-6.7 score on a scale Standard Deviation 6.49	-7.0 score on a scale Standard Deviation 4.77	-6.9 score on a scale Standard Deviation 5.79
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 18	-15.5 score on a scale Standard Deviation 15.03	-24.0 score on a scale Standard Deviation 20.50	-16.9 score on a scale Standard Deviation 15.12	-19.9 score on a scale Standard Deviation 19.78
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 18	-17.3 score on a scale Standard Deviation 10.36	-17.5 score on a scale Standard Deviation 13.01	-13.9 score on a scale Standard Deviation 10.45	-15.0 score on a scale Standard Deviation 10.45
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 18	-1.5 score on a scale Standard Deviation 4.24	-7.8 score on a scale Standard Deviation 12.94	-9.8 score on a scale Standard Deviation 8.74	-6.1 score on a scale Standard Deviation 9.38
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 36	-18.0 score on a scale	-47.5 score on a scale Standard Deviation 12.53	-54.3 score on a scale Standard Deviation 15.04	-57.0 score on a scale Standard Deviation 29.94
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 39	4.0 score on a scale	-5.3 score on a scale Standard Deviation 4.39	-0.5 score on a scale Standard Deviation 10.61	-7.5 score on a scale Standard Deviation 3.50
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 39	-12.0 score on a scale	-13.1 score on a scale Standard Deviation 7.90	-6.0 score on a scale Standard Deviation 42.43	-22.5 score on a scale Standard Deviation 14.78
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 39	-4.0 score on a scale	-15.4 score on a scale Standard Deviation 5.97	-7.0 score on a scale Standard Deviation 15.56	-16.6 score on a scale Standard Deviation 10.02
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 42	—	-12.0 score on a scale	-14.0 score on a scale Standard Deviation 19.80	-27.4 score on a scale Standard Deviation 13.55
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 3	-7.1 score on a scale Standard Deviation 5.18	-6.8 score on a scale Standard Deviation 5.57	-5.5 score on a scale Standard Deviation 5.41	-6.4 score on a scale Standard Deviation 5.84
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 3	-23.7 score on a scale Standard Deviation 17.41	-18.5 score on a scale Standard Deviation 21.57	-13.5 score on a scale Standard Deviation 17.28	-16.9 score on a scale Standard Deviation 17.78
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 3	-16.1 score on a scale Standard Deviation 11.47	-13.6 score on a scale Standard Deviation 13.48	-9.9 score on a scale Standard Deviation 10.26	-12.6 score on a scale Standard Deviation 11.90
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 3	-7.3 score on a scale Standard Deviation 10.15	-6.3 score on a scale Standard Deviation 10.19	-6.4 score on a scale Standard Deviation 9.42	-5.3 score on a scale Standard Deviation 8.80
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 3	-54.1 score on a scale Standard Deviation 32.78	-45.2 score on a scale Standard Deviation 40.50	-35.2 score on a scale Standard Deviation 30.97	-41.3 score on a scale Standard Deviation 34.02
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 6	-7.0 score on a scale Standard Deviation 4.62	-5.4 score on a scale Standard Deviation 6.05	-6.2 score on a scale Standard Deviation 4.93	-5.9 score on a scale Standard Deviation 5.67
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 6	-23.6 score on a scale Standard Deviation 12.84	-19.2 score on a scale Standard Deviation 24.44	-16.1 score on a scale Standard Deviation 15.55	-15.9 score on a scale Standard Deviation 17.62
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 6	-7.2 score on a scale Standard Deviation 7.75	-6.8 score on a scale Standard Deviation 10.29	-7.5 score on a scale Standard Deviation 8.40	-5.6 score on a scale Standard Deviation 8.78
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 6	-14.4 score on a scale Standard Deviation 10.54	-12.5 score on a scale Standard Deviation 13.35	-11.6 score on a scale Standard Deviation 11.27	-11.8 score on a scale Standard Deviation 13.21
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 6	-52.2 score on a scale Standard Deviation 26.54	-44.0 score on a scale Standard Deviation 41.31	-41.4 score on a scale Standard Deviation 28.50	-39.2 score on a scale Standard Deviation 34.04
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 9	-6.4 score on a scale Standard Deviation 4.30	-6.8 score on a scale Standard Deviation 5.03	-6.5 score on a scale Standard Deviation 6.33	-5.0 score on a scale Standard Deviation 5.97
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 9	-17.7 score on a scale Standard Deviation 15.79	-22.6 score on a scale Standard Deviation 21.97	-15.7 score on a scale Standard Deviation 16.05	-13.7 score on a scale Standard Deviation 16.30
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 9	-13.9 score on a scale Standard Deviation 9.27	-15.6 score on a scale Standard Deviation 11.85	-11.7 score on a scale Standard Deviation 12.00	-11.2 score on a scale Standard Deviation 12.98
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 9	-8.1 score on a scale Standard Deviation 8.72	-7.1 score on a scale Standard Deviation 10.94	-9.2 score on a scale Standard Deviation 8.92	-6.6 score on a scale Standard Deviation 8.88
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 9	-46.1 score on a scale Standard Deviation 25.55	-52.2 score on a scale Standard Deviation 39.56	-43.2 score on a scale Standard Deviation 30.59	-36.5 score on a scale Standard Deviation 33.44
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 12	-4.2 score on a scale Standard Deviation 5.57	-6.6 score on a scale Standard Deviation 5.91	-6.8 score on a scale Standard Deviation 4.81	-5.9 score on a scale Standard Deviation 6.35
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 12	-11.1 score on a scale Standard Deviation 14.71	-19.1 score on a scale Standard Deviation 19.43	-18.2 score on a scale Standard Deviation 16.54	-16.1 score on a scale Standard Deviation 18.18
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 12	-9.5 score on a scale Standard Deviation 12.63	-14.4 score on a scale Standard Deviation 13.11	-11.6 score on a scale Standard Deviation 10.50	-11.8 score on a scale Standard Deviation 13.08
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 12	-2.8 score on a scale Standard Deviation 6.87	-7.0 score on a scale Standard Deviation 11.80	-8.5 score on a scale Standard Deviation 8.85	-6.7 score on a scale Standard Deviation 8.40
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 12	-27.6 score on a scale Standard Deviation 28.46	-47.0 score on a scale Standard Deviation 40.33	-45.2 score on a scale Standard Deviation 28.69	-40.4 score on a scale Standard Deviation 34.34
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 15	-5.5 score on a scale Standard Deviation 3.87	-7.2 score on a scale Standard Deviation 6.26	-7.2 score on a scale Standard Deviation 4.91	-6.2 score on a scale Standard Deviation 6.05
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 15	-14.4 score on a scale Standard Deviation 15.11	-20.7 score on a scale Standard Deviation 19.65	-17.3 score on a scale Standard Deviation 14.86	-16.5 score on a scale Standard Deviation 18.43
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 15	-13.4 score on a scale Standard Deviation 10.59	-16.5 score on a scale Standard Deviation 12.78	-13.2 score on a scale Standard Deviation 11.45	-13.5 score on a scale Standard Deviation 12.34
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 15	-4.5 score on a scale Standard Deviation 5.87	-6.3 score on a scale Standard Deviation 12.96	-9.9 score on a scale Standard Deviation 8.84	-6.7 score on a scale Standard Deviation 8.15
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 27	-6.4 score on a scale Standard Deviation 6.80	-7.6 score on a scale Standard Deviation 5.69	-8.8 score on a scale Standard Deviation 5.51	-6.7 score on a scale Standard Deviation 3.79
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 27	1.8 score on a scale Standard Deviation 5.85	-10.3 score on a scale Standard Deviation 13.75	-9.0 score on a scale Standard Deviation 7.65	-5.9 score on a scale Standard Deviation 7.86
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 27	-35.4 score on a scale Standard Deviation 28.79	-59.6 score on a scale Standard Deviation 37.18	-51.6 score on a scale Standard Deviation 32.26	-51.8 score on a scale Standard Deviation 29.04
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 30	-14.5 score on a scale Standard Deviation 9.85	-17.7 score on a scale Standard Deviation 10.32	-16.7 score on a scale Standard Deviation 14.51	-13.5 score on a scale Standard Deviation 13.45
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 30	-2.3 score on a scale Standard Deviation 2.87	-8.9 score on a scale Standard Deviation 13.70	-6.8 score on a scale Standard Deviation 9.15	-4.9 score on a scale Standard Deviation 9.60
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 33	-8.5 score on a scale Standard Deviation 4.95	-6.8 score on a scale Standard Deviation 3.12	-11.0 score on a scale Standard Deviation 4.32	-5.7 score on a scale Standard Deviation 5.99
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 33	-24.0 score on a scale Standard Deviation 16.97	-11.5 score on a scale Standard Deviation 23.07	-42.0 score on a scale Standard Deviation 13.66	-15.7 score on a scale Standard Deviation 14.33
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 33	-14.0 score on a scale Standard Deviation 11.31	-15.7 score on a scale Standard Deviation 12.46	-18.0 score on a scale Standard Deviation 17.05	-12.0 score on a scale Standard Deviation 8.41
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 33	-46.5 score on a scale Standard Deviation 33.23	-39.4 score on a scale Standard Deviation 34.32	-79.3 score on a scale Standard Deviation 37.29	-36.4 score on a scale Standard Deviation 33.14
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 18	-40.0 score on a scale Standard Deviation 30.85	-56.0 score on a scale Standard Deviation 42.08	-47.6 score on a scale Standard Deviation 25.64	-47.8 score on a scale Standard Deviation 36.62
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 21	-7.0 score on a scale Standard Deviation 4.69	-6.9 score on a scale Standard Deviation 6.84	-7.9 score on a scale Standard Deviation 5.71	-6.7 score on a scale Standard Deviation 5.66
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 21	-20.0 score on a scale Standard Deviation 8.00	-22.7 score on a scale Standard Deviation 21.11	-18.3 score on a scale Standard Deviation 14.44	-19.9 score on a scale Standard Deviation 18.08
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 21	-11.7 score on a scale Standard Deviation 10.84	-18.7 score on a scale Standard Deviation 13.19	-15.2 score on a scale Standard Deviation 11.67	-13.4 score on a scale Standard Deviation 12.71
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 21	-2.5 score on a scale Standard Deviation 3.99	-10.0 score on a scale Standard Deviation 13.05	-9.9 score on a scale Standard Deviation 9.95	-7.2 score on a scale Standard Deviation 8.03
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 21	-41.2 score on a scale Standard Deviation 12.80	-58.3 score on a scale Standard Deviation 45.11	-51.4 score on a scale Standard Deviation 27.49	-47.1 score on a scale Standard Deviation 34.49
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 24	-6.0 score on a scale Standard Deviation 5.66	-7.5 score on a scale Standard Deviation 5.18	-8.3 score on a scale Standard Deviation 5.50	-5.5 score on a scale Standard Deviation 5.55
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 24	-16.7 score on a scale Standard Deviation 13.25	-24.3 score on a scale Standard Deviation 19.04	-19.6 score on a scale Standard Deviation 15.95	-17.7 score on a scale Standard Deviation 18.19
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 24	-13.3 score on a scale Standard Deviation 10.25	-19.2 score on a scale Standard Deviation 9.87	-14.2 score on a scale Standard Deviation 11.82	-13.3 score on a scale Standard Deviation 9.24
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 24	1.5 score on a scale Standard Deviation 6.50	-8.9 score on a scale Standard Deviation 12.01	-8.9 score on a scale Standard Deviation 8.10	-6.0 score on a scale Standard Deviation 8.68
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 24	-34.5 score on a scale Standard Deviation 27.24	-59.9 score on a scale Standard Deviation 34.30	-51.0 score on a scale Standard Deviation 27.96	-42.6 score on a scale Standard Deviation 33.62
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 27	-19.2 score on a scale Standard Deviation 15.07	-23.5 score on a scale Standard Deviation 19.26	-17.4 score on a scale Standard Deviation 18.65	-24.7 score on a scale Standard Deviation 19.17
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 27	-11.6 score on a scale Standard Deviation 7.92	-18.2 score on a scale Standard Deviation 10.48	-16.5 score on a scale Standard Deviation 11.91	-14.5 score on a scale Standard Deviation 11.25
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 30	-10.0 score on a scale Standard Deviation 4.24	-8.3 score on a scale Standard Deviation 5.79	-8.8 score on a scale Standard Deviation 5.34	-6.8 score on a scale Standard Deviation 4.97
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 30	-17.0 score on a scale Standard Deviation 17.70	-19.6 score on a scale Standard Deviation 20.55	-23.0 score on a scale Standard Deviation 16.81	-22.2 score on a scale Standard Deviation 16.34
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score Total Score Month 30	-43.8 score on a scale Standard Deviation 30.91	-54.5 score on a scale Standard Deviation 39.26	-55.3 score on a scale Standard Deviation 29.39	-47.7 score on a scale Standard Deviation 31.41
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score SE Score Month 33	0.0 score on a scale Standard Deviation 0.00	-5.4 score on a scale Standard Deviation 8.58	-8.3 score on a scale Standard Deviation 7.50	-3.0 score on a scale Standard Deviation 11.16
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score VE Score Month 36	-6.0 score on a scale	-7.3 score on a scale Standard Deviation 3.65	-7.7 score on a scale Standard Deviation 5.03	-7.9 score on a scale Standard Deviation 7.06
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PH Score Month 36	-4.0 score on a scale	-14.3 score on a scale Standard Deviation 9.26	-30.7 score on a scale Standard Deviation 6.11	-26.5 score on a scale Standard Deviation 16.13
Effect of SPN810 on Retrospective-Modified Overt Aggression Scale (R-MOAS) Total Score PR Score Month 36	-8.0 score on a scale	-17.2 score on a scale Standard Deviation 6.41	-12.0 score on a scale Standard Deviation 6.00	-17.1 score on a scale Standard Deviation 9.30

PRIMARY outcome

Timeframe: 20-time points: Week 2 (V2), Week 4 (V3), Week 8 (V4), Months 3 (V5), 6 (V6), 9 (V7), 12 (V8), 15 (V9),18 (V10), 21 (V11), 24 (V12), 27 (V13), 30 (V14), 33 (V15), 36 (V16), 39 (V17), 42 (V18), 45 (V19), 48 (V20) and month 60 (Visit 24).

Population: Safety Population: Safety population is defined as all subjects who received at least 1 dose of study drug during the study.

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 from baseline to each visit during the study. The baseline score represents the total score at the last visit of each double-blind study.

Outcome measures

Outcome measures
Measure	<18 mg SPN-810 n=38 Participants Subjects treated with 6, 12 or 15 mg/day SPN-810	18 mg to < 24 mg SPN-810 n=159 Participants Subjects treated with 18 mg/day or 21 mg/day SPN-810	24 mg to < 36 mg SPN-810 n=131 Participants Subjects treated with 24, 27 or 30 mg/day SPN-810	36 mg to ≤54 mg SPN-810 n=163 Participants Subjects treated with 36, 42, 45, 48 or 54 mg/day SPN-810
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 12	-1.5 score on a scale Standard Deviation 1.13	-2.3 score on a scale Standard Deviation 0.96	-2.0 score on a scale Standard Deviation 1.01	-1.8 score on a scale Standard Deviation 1.03
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 24	-2.5 score on a scale Standard Deviation 1.05	-2.3 score on a scale Standard Deviation 0.89	-2.1 score on a scale Standard Deviation 1.13	-1.9 score on a scale Standard Deviation 0.98
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 30	-2.0 score on a scale Standard Deviation 1.83	-2.4 score on a scale Standard Deviation 0.88	-2.0 score on a scale Standard Deviation 1.13	-2.2 score on a scale Standard Deviation 0.99
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Week 2	-1.2 score on a scale Standard Deviation 1.33	-1.8 score on a scale Standard Deviation 1.13	-1.0 score on a scale Standard Deviation 0.94	-1.0 score on a scale Standard Deviation 0.95
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Week 4	-1.6 score on a scale Standard Deviation 1.26	-2.1 score on a scale Standard Deviation 1.10	-1.2 score on a scale Standard Deviation 1.12	-1.3 score on a scale Standard Deviation 1.06
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Week 8	-2.0 score on a scale Standard Deviation 1.20	-2.1 score on a scale Standard Deviation 1.18	-1.4 score on a scale Standard Deviation 1.13	-1.5 score on a scale Standard Deviation 1.02
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 3	-1.9 score on a scale Standard Deviation 1.37	-2.2 score on a scale Standard Deviation 1.08	-1.5 score on a scale Standard Deviation 1.15	-1.6 score on a scale Standard Deviation 0.98
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 6	-2.0 score on a scale Standard Deviation 0.95	-2.2 score on a scale Standard Deviation 1.07	-1.5 score on a scale Standard Deviation 0.95	-1.8 score on a scale Standard Deviation 0.95
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 9	-1.9 score on a scale Standard Deviation 0.90	-2.2 score on a scale Standard Deviation 1.02	-1.8 score on a scale Standard Deviation 0.92	-1.8 score on a scale Standard Deviation 0.97
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 15	-1.7 score on a scale Standard Deviation 1.25	-2.3 score on a scale Standard Deviation 0.93	-1.9 score on a scale Standard Deviation 0.90	-1.8 score on a scale Standard Deviation 0.97
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 18	-1.5 score on a scale Standard Deviation 1.51	-2.1 score on a scale Standard Deviation 1.03	-2.0 score on a scale Standard Deviation 1.08	-2.0 score on a scale Standard Deviation 0.90
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 21	-2.3 score on a scale Standard Deviation 1.03	-2.2 score on a scale Standard Deviation 1.01	-1.9 score on a scale Standard Deviation 1.03	-1.9 score on a scale Standard Deviation 0.92
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 27	-1.8 score on a scale Standard Deviation 1.48	-2.2 score on a scale Standard Deviation 0.87	-1.9 score on a scale Standard Deviation 1.03	-2.0 score on a scale Standard Deviation 0.95
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 33	-3.5 score on a scale Standard Deviation 0.71	-2.3 score on a scale Standard Deviation 1.03	-2.8 score on a scale Standard Deviation 1.71	-1.8 score on a scale Standard Deviation 0.89
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 36	-4.0 score on a scale	-2.6 score on a scale Standard Deviation 0.79	-1.7 score on a scale Standard Deviation 0.58	-1.9 score on a scale Standard Deviation 0.73
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 39	-4.0 score on a scale	-2.7 score on a scale Standard Deviation 0.95	-1.5 score on a scale Standard Deviation 0.71	-2.1 score on a scale Standard Deviation 0.70
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 42	—	-3.0 score on a scale Standard Deviation 0.00	-2.0 score on a scale Standard Deviation 0.00	-2.0 score on a scale Standard Deviation 1.15
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 45	—	-4.0 score on a scale	—	-2.0 score on a scale Standard Deviation 0.00
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 48	—	—	—	-3.0 score on a scale
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Severity Scale (CGI-S) Month 60	—	—	-1.0 score on a scale	-3.0 score on a scale

PRIMARY outcome

Population: Safety Population: Safety population is defined as all subjects who received at least 1 dose of study drug during the study.

The Clinical Global Impression - Improvement Scale (CGI-I) is a clinician's assessment of how much the IA behaviors have improved or worsened relative to a baseline state at the beginning of treatment. CGI-I was evaluated by the Investigator at each visit on a 7-point scale with 1=Very much improved, 2= Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Data represent the score at each visit during the study.

Outcome measures

Outcome measures
Measure	<18 mg SPN-810 n=38 Participants Subjects treated with 6, 12 or 15 mg/day SPN-810	18 mg to < 24 mg SPN-810 n=159 Participants Subjects treated with 18 mg/day or 21 mg/day SPN-810	24 mg to < 36 mg SPN-810 n=131 Participants Subjects treated with 24, 27 or 30 mg/day SPN-810	36 mg to ≤54 mg SPN-810 n=163 Participants Subjects treated with 36, 42, 45, 48 or 54 mg/day SPN-810
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Week 4	2.1 score on a scale Standard Deviation 1.00	1.9 score on a scale Standard Deviation 0.94	2.6 score on a scale Standard Deviation 1.18	2.7 score on a scale Standard Deviation 1.02
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Week 8	1.9 score on a scale Standard Deviation 0.80	1.9 score on a scale Standard Deviation 1.05	2.4 score on a scale Standard Deviation 0.97	2.5 score on a scale Standard Deviation 1.05
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 36	1.0 score on a scale	1.5 score on a scale Standard Deviation 0.52	2.3 score on a scale Standard Deviation 0.58	1.9 score on a scale Standard Deviation 0.73
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 39	1.0 score on a scale	1.3 score on a scale Standard Deviation 0.49	2.5 score on a scale Standard Deviation 0.71	1.5 score on a scale Standard Deviation 0.52
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 45	—	1.0 score on a scale	—	1.5 score on a scale Standard Deviation 0.71
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Week 2	2.7 score on a scale Standard Deviation 1.25	2.1 score on a scale Standard Deviation 0.96	2.9 score on a scale Standard Deviation 1.19	2.9 score on a scale Standard Deviation 0.98
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 3	1.9 score on a scale Standard Deviation 0.98	1.8 score on a scale Standard Deviation 0.84	2.4 score on a scale Standard Deviation 1.11	2.3 score on a scale Standard Deviation 1.06
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 6	1.7 score on a scale Standard Deviation 0.66	1.7 score on a scale Standard Deviation 0.78	2.2 score on a scale Standard Deviation 1.13	2.2 score on a scale Standard Deviation 1.02
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 9	1.8 score on a scale Standard Deviation 0.65	1.7 score on a scale Standard Deviation 0.69	2.0 score on a scale Standard Deviation 0.80	2.1 score on a scale Standard Deviation 0.91
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 12	2.5 score on a scale Standard Deviation 1.33	1.8 score on a scale Standard Deviation 1.10	1.9 score on a scale Standard Deviation 0.80	2.1 score on a scale Standard Deviation 0.92
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 15	2.3 score on a scale Standard Deviation 1.77	1.8 score on a scale Standard Deviation 1.11	2.0 score on a scale Standard Deviation 0.76	2.1 score on a scale Standard Deviation 0.80
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 18	2.6 score on a scale Standard Deviation 2.07	1.9 score on a scale Standard Deviation 1.11	1.9 score on a scale Standard Deviation 0.71	1.9 score on a scale Standard Deviation 0.64
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 21	1.5 score on a scale Standard Deviation 0.55	1.7 score on a scale Standard Deviation 0.67	2.0 score on a scale Standard Deviation 0.77	1.9 score on a scale Standard Deviation 0.76
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 24	1.2 score on a scale Standard Deviation 0.41	1.7 score on a scale Standard Deviation 0.60	2.0 score on a scale Standard Deviation 0.72	1.8 score on a scale Standard Deviation 0.98
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 27	2.4 score on a scale Standard Deviation 1.52	1.6 score on a scale Standard Deviation 0.49	1.7 score on a scale Standard Deviation 0.69	1.9 score on a scale Standard Deviation 1.00
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 30	2.3 score on a scale Standard Deviation 1.89	1.5 score on a scale Standard Deviation 0.51	1.8 score on a scale Standard Deviation 0.75	1.9 score on a scale Standard Deviation 1.21
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 33	1.0 score on a scale Standard Deviation 0.00	1.5 score on a scale Standard Deviation 0.64	1.8 score on a scale Standard Deviation 0.96	1.9 score on a scale Standard Deviation 0.66
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 42	—	1.5 score on a scale Standard Deviation 0.71	2.0 score on a scale Standard Deviation 0.00	1.7 score on a scale Standard Deviation 1.11
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 48	—	—	—	1.0 score on a scale
Effect of SPN810 on Impulsive Aggression (IA) Measured by Clinical Global Impression - Improvement Scale (CGI-I) Month 60	—	—	3.0 score on a scale	1.0 score on a scale

Adverse Events

<18 mg SPN-810

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

18 mg to < 24 mg SPN-810

Serious events: 5 serious events

Other events: 56 other events

Deaths: 0 deaths

24 mg to < 36 mg SPN-810

Serious events: 5 serious events

Other events: 56 other events

Deaths: 0 deaths

36 mg to ≤54 mg SPN-810

Serious events: 9 serious events

Other events: 66 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	<18 mg SPN-810 n=38 participants at risk Subjects treated with 6, 12 or 15 mg/day SPN-810	18 mg to < 24 mg SPN-810 n=159 participants at risk Subjects treated with 18 mg/day or 21 mg/day SPN-810	24 mg to < 36 mg SPN-810 n=131 participants at risk Subjects treated with 24, 27 or 30 mg/day SPN-810	36 mg to ≤54 mg SPN-810 n=163 participants at risk Subjects treated with 36, 42, 45, 48 or 54 mg/day SPN-810
Psychiatric disorders Suicidal Ideation	0.00% 0/38 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	1.3% 2/159 • Number of events 2 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	2.3% 3/131 • Number of events 3 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	1.2% 2/163 • Number of events 2 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.
Psychiatric disorders Aggression	2.6% 1/38 • Number of events 1 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	1.9% 3/159 • Number of events 4 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/131 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	1.2% 2/163 • Number of events 2 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.
Psychiatric disorders Oppositional Defiant Disorder	2.6% 1/38 • Number of events 1 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/159 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/131 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/163 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.
Psychiatric disorders Suicide Attempt	0.00% 0/38 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/159 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.76% 1/131 • Number of events 1 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/163 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.
Infections and infestations Appendicitis	0.00% 0/38 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/159 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/131 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.61% 1/163 • Number of events 1 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.
Psychiatric disorders Agitation	0.00% 0/38 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/159 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/131 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.61% 1/163 • Number of events 2 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.
Psychiatric disorders Mental Status Changes	0.00% 0/38 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/159 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/131 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.61% 1/163 • Number of events 1 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.
Infections and infestations Infection	0.00% 0/38 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/159 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/131 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.61% 1/163 • Number of events 1 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.
Infections and infestations Infectious Mononucleosis	0.00% 0/38 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/159 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.76% 1/131 • Number of events 1 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/163 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.
Infections and infestations Pyelonephritis	0.00% 0/38 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/159 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/131 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.61% 1/163 • Number of events 1 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.
Nervous system disorders Brain Mass	2.6% 1/38 • Number of events 1 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/159 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/131 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.	0.00% 0/163 • Adverse events were collected at each study visit: Visit 1 (last visit in the double-blind study), weeks 2,4 and 8, and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 60 (months). Adverse events reporting pertains to the Safety Population, defined as all subjects who received at least 1 dose of study drug during the study.

Other adverse events

Additional Information

Gianpiera Ceresoli-Borroni/ Director Clinical Development

Supernus Pharmaceuticals

Phone: 3018382521

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place