Trial Outcomes & Findings for Open-label Long-Term Safety and Efficacy of SPN-812 (Viloxazine Extended-release Capsule) in Adults With ADHD (NCT NCT04143217)

Results Overview

The percent of subjects who took at least one dose of SPN-812 (Safety Population; N) and who reported at least one Adverse Event (n). The percent is calculated by dividing "the number of subjects who reported at least one Adverse Event (n)" by "the number of subjects in the Safety Population (N)" and multiplying the product by 100. The higher the percentage, the higher the incidence in the Safety Population

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

159 participants

Primary outcome timeframe

Up to 156 weeks

Results posted on

2024-02-13

Participant Flow

Participant milestones

Participant milestones
Measure	Open-Label Treatment SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Overall Study STARTED	159
Overall Study Not Treated	5
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	133

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-Label Treatment SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Overall Study Withdrawal by Subject	42
Overall Study Adverse Event	29
Overall Study Lost to Follow-up	29
Overall Study Lack of Efficacy	15
Overall Study Physician Decision	1
Overall Study Non-Compliance With Study Drug	6
Overall Study Other, Multiple Categories	11

Baseline Characteristics

Open-label Long-Term Safety and Efficacy of SPN-812 (Viloxazine Extended-release Capsule) in Adults With ADHD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Age, Continuous	36.3 years STANDARD_DEVIATION 10.25 • n=5 Participants
Age, Customized 18 to 44 years of age	119 Participants n=5 Participants
Age, Customized 45 to 65 years of age	40 Participants n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants
Sex: Female, Male Male	82 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	128 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants
Race (NIH/OMB) White	133 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	159 participants n=5 Participants
Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score	37.9 units on a scale STANDARD_DEVIATION 6.34 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 156 weeks

Population: Safety Population, defined as subjects who signed Informed Consent and took at least one dose of SPN-812.

The percent of subjects who took at least one dose of SPN-812 (Safety Population; N) and who reported at least one Adverse Event (n). The percent is calculated by dividing "the number of subjects who reported at least one Adverse Event (n)" by "the number of subjects in the Safety Population (N)" and multiplying the product by 100. The higher the percentage, the higher the incidence in the Safety Population

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Incidence of Adverse Events	72.3 percentage of subjects

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid AISRS assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

A secondary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) Total score by visit. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. The sum of the ratings of all 18 items yields the raw Total score (range: 0-54; the higher the Total score, the more severe the ADHD symptoms). Post-baseline raw Total scores are converted to a change from baseline Total score. A lower change from baseline AISRS Total Score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Raw score; Baseline	37.9 units on a scale Standard Deviation 6.34
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 2	-11.4 units on a scale Standard Deviation 9.50
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 4	-15.0 units on a scale Standard Deviation 10.13
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 12	-17.6 units on a scale Standard Deviation 10.69
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 20	-18.7 units on a scale Standard Deviation 11.46
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 28	-19.9 units on a scale Standard Deviation 9.88
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 36	-20.9 units on a scale Standard Deviation 10.39
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 44	-21.1 units on a scale Standard Deviation 10.27
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 52	-22.0 units on a scale Standard Deviation 10.40
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 60	-22.6 units on a scale Standard Deviation 11.34
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 68	-22.1 units on a scale Standard Deviation 11.32
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 76	-24.3 units on a scale Standard Deviation 10.64
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 84	-22.8 units on a scale Standard Deviation 10.86
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 92	-24.2 units on a scale Standard Deviation 11.94
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 100	-23.7 units on a scale Standard Deviation 11.72
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 108	-26.3 units on a scale Standard Deviation 11.29
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 116	-25.9 units on a scale Standard Deviation 12.41
The Effect of SPN-812 on Overall ADHD Symptoms as Measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Change from baseline score; Week 124	-21.5 units on a scale Standard Deviation 16.26

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid CGI-S assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Clinical Global Impression - Severity of Illness (CGI-S) score at Week 6. The CGI-S is a single item clinician-rated assessment of the severity of subject's condition (ADHD symptoms) in relation to the clinician's total experience with patients with ADHD. The CGI-S is evaluated on a 7-point scale with 1 = Normal, not at all ill, asymptomatic, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Among the most extremely ill patients (the higher the score, the more severe the overall ADHD symptoms). Post-baseline (raw) CGI-S scores are converted to a change from baseline score. A lower change from baseline CGI-S score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Raw score; Baseline	4.6 units on a scale Standard Deviation 0.60
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 2	-1.0 units on a scale Standard Deviation 0.99
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 4	-1.3 units on a scale Standard Deviation 1.08
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 12	-1.6 units on a scale Standard Deviation 1.11
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 20	-1.8 units on a scale Standard Deviation 1.21
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 28	-1.8 units on a scale Standard Deviation 1.15
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 36	-2.0 units on a scale Standard Deviation 1.21
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 44	-2.0 units on a scale Standard Deviation 1.17
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 52	-2.1 units on a scale Standard Deviation 1.25
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 60	-2.2 units on a scale Standard Deviation 1.25
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 68	-2.1 units on a scale Standard Deviation 1.31
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 76	-2.4 units on a scale Standard Deviation 1.17
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 84	-2.3 units on a scale Standard Deviation 1.17
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 92	-2.5 units on a scale Standard Deviation 1.36
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 100	-2.3 units on a scale Standard Deviation 1.11
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 108	-2.7 units on a scale Standard Deviation 1.12
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 116	-2.4 units on a scale Standard Deviation 1.30
The Effect of SPN-812 on Global Assessment of ADHD Symptom Severity as Measured by the Clinical Global Impression - Severity of Illness (CGI-S) Change from baseline score; Week 124	-1.5 units on a scale Standard Deviation 1.91

SECONDARY outcome

Timeframe: Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, percent is based on number of "responders" (m; CGI-S score of 1 or 2) and number of subjects analyzed (n; subjects with valid CGI-S assessment at baseline \[pre-dosing\] and at respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate by visit. The CGI-S Responder Rate was defined as the percent of subjects with a CGI-S score of 1 or 2 ("responders"). The CGI-S is a single item clinician-rated assessment of the severity of subject's condition (ADHD symptoms) in relation to the clinician's total experience with patients with ADHD. The CGI-S is evaluated on a 7-point scale with 1 = Normal, not at all ill, asymptomatic, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Among the most extremely ill patients. The responder rate (percent) is calculated by dividing "the number of 'responders' (m)" by "the number of subjects analyzed at the respective Visit/Week (n)" and multiplying the product by 100. Responder Rate values range from 0 to 100%. A percent \>50% represents a greater number of "responders" versus "non-responders".

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 2	16.4 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 4	23.5 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 12	29.5 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 20	36.8 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 28	42.0 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 36	47.8 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 44	42.4 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 52	56.9 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 60	53.8 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 68	52.8 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 76	60.6 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 84	55.2 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 92	68.0 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 100	61.5 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 108	66.7 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 116	62.5 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Severity of Illness (CGI-S) Responder Rate Percent of subjects; Week 124	25.0 percentage of subjects

SECONDARY outcome

Timeframe: Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the total number of subjects analyzed (n; subjects with a valid CGI-I assessment at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the Clinical Global Impression - Improvement (CGI-I) score by visit. The CGI-I scale is a single item clinician-rated assessment of how much the subject's condition (ADHD) has improved, worsened or has not changed relative to his/her baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point scale from 1 to 7, where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved", 4 = "no change", 5 = "minimally worse", 6 = "much worse", and 7 = "very much worse". A CGI-I score \<4 represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 2	2.9 units on a scale Standard Deviation 0.96
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 4	2.6 units on a scale Standard Deviation 0.97
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 12	2.4 units on a scale Standard Deviation 1.02
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 20	2.2 units on a scale Standard Deviation 1.00
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 28	2.2 units on a scale Standard Deviation 0.93
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 36	1.9 units on a scale Standard Deviation 0.93
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 44	1.9 units on a scale Standard Deviation 0.88
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 52	1.9 units on a scale Standard Deviation 1.12
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 60	1.8 units on a scale Standard Deviation 0.87
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 68	1.8 units on a scale Standard Deviation 0.97
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 76	1.8 units on a scale Standard Deviation 0.85
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 84	1.9 units on a scale Standard Deviation 0.88
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 92	1.8 units on a scale Standard Deviation 1.03
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 100	1.8 units on a scale Standard Deviation 0.90
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 108	1.7 units on a scale Standard Deviation 0.71
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 116	1.8 units on a scale Standard Deviation 0.71
The Effect of SPN-812 on Global Assessment of Improvement of ADHD Symptoms as Measured by the Clinical Global Impression - Improvement Scale (CGI-I) Scale Score; Week 124	2.5 units on a scale Standard Deviation 1.29

SECONDARY outcome

Timeframe: Weeks 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, the percent is based on number of "responders" (m; CGI-I score of 1 or 2) and number of subjects analyzed (n; subjects with a valid CGI-I assessment at respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional endpoint was Clinical Global Impression - Improvement (CGI-I) Responder Rate by visit. The CGI-I Responder Rate was defined as the percent of subjects with a CGI-I score of 1 or 2 ("responders"). The CGI-I scale is a single item clinician-rated assessment of how much the subject's condition (ADHD) has improved, worsened or has not changed relative to his/her baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point scale from 1 to 7, where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved", 4 = "no change", 5 = "minimally worse", 6 = "much worse", and 7 = "very much worse". The responder rate (percent) is calculated by dividing "the number of 'responders' (m)" by "the number of subjects analyzed at the respective Visit/Week (n)" and multiplying the product by 100. Responder Rate values range from 0 to 100%. A percent \>50% represents a greater number of "responders" versus "non-responders".

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 2	32.9 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 4	47.7 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 12	61.6 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 20	68.4 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 28	70.4 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 36	76.1 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 44	79.7 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 52	80.4 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 60	84.6 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 68	77.8 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 76	84.8 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 84	82.8 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 92	80.0 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 100	84.6 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 108	88.9 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 116	87.5 percentage of subjects
The Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Responder Rate Percent of subjects; Week 124	50.0 percentage of subjects

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid GAD-7 assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Generalized Anxiety Disorder 7-Item (GAD-7) Total Score by visit. The GAD-7 is a self-reported 7-item questionnaire for screening and measuring the severity of generalized anxiety disorder. The subject rates each item on 4-point scale (0-3), where 0 = "Not at all", 1 = "Several days", 2 = "Over half the days", and 3 = "Nearly every day". The sum of the 7 items yields a raw GAD-7 Total score (range between 0 to 21); the higher the GAD-7 Total score, the more severe the symptoms of anxiety. Post-baseline raw GAD-7 Total scores are converted to a change from baseline score. A lower change from baseline GAD-7 Total score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Raw score; Baseline	5.9 units on a scale Standard Deviation 4.47
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 2	-1.2 units on a scale Standard Deviation 3.93
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 4	-1.6 units on a scale Standard Deviation 4.40
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 12	-1.7 units on a scale Standard Deviation 4.63
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 20	-2.0 units on a scale Standard Deviation 3.99
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 28	-2.0 units on a scale Standard Deviation 3.90
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 36	-1.3 units on a scale Standard Deviation 4.43
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 44	-2.1 units on a scale Standard Deviation 3.50
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 52	-2.0 units on a scale Standard Deviation 4.25
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 60	-1.7 units on a scale Standard Deviation 3.87
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 68	-2.4 units on a scale Standard Deviation 3.87
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 76	-2.6 units on a scale Standard Deviation 3.41
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 84	-2.4 units on a scale Standard Deviation 4.04
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 92	-3.2 units on a scale Standard Deviation 3.40
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 100	-3.2 units on a scale Standard Deviation 3.74
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 108	-3.1 units on a scale Standard Deviation 4.14
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 116	-3.5 units on a scale Standard Deviation 4.00
Effect of SPN-812 on Symptoms of Anxiety as Measured by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale Change from baseline score; Week 124	-3.8 units on a scale Standard Deviation 5.56

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid AISRS assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to the Safety Population.

An additional secondary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) "Hyperactivity/Impulsivity" (H/I) subscale score. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and H/I (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. The sum of the nine H/I items yields the raw H/I subscale score (range: 0-27; the higher the H/I subscale score, the more severe the H/I symptoms). Post-baseline raw H/I subscale scores are converted to a change from baseline score. A lower change from baseline H/I subscale score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 100	-11.1 units on a scale Standard Deviation 5.25
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 108	-12.2 units on a scale Standard Deviation 4.94
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Raw score; Baseline	16.2 units on a scale Standard Deviation 4.92
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 2	-5.3 units on a scale Standard Deviation 5.35
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 4	-7.1 units on a scale Standard Deviation 5.27
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 12	-8.1 units on a scale Standard Deviation 5.67
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 20	-8.4 units on a scale Standard Deviation 5.83
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 28	-8.7 units on a scale Standard Deviation 5.30
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 36	-9.7 units on a scale Standard Deviation 5.80
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 44	-10.1 units on a scale Standard Deviation 5.28
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 52	-10.2 units on a scale Standard Deviation 5.84
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 60	-10.1 units on a scale Standard Deviation 5.96
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 68	-10.4 units on a scale Standard Deviation 5.52
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 76	-11.1 units on a scale Standard Deviation 5.31
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 84	-10.5 units on a scale Standard Deviation 5.42
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 92	-11.1 units on a scale Standard Deviation 5.34
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 116	-11.9 units on a scale Standard Deviation 4.97
Effect of SPN-812 on Hyperactivity/Impulsivity (H/I) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating H/I Subscale Change from baseline score; Week 124	-10.3 units on a scale Standard Deviation 7.93

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid AISRS assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to the Safety Population.

An additional secondary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) "Inattention" (IA) subscale score. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. The sum of the nine IA items yields the raw IA subscale score (range: 0-27; the higher the IA subscale score, the more severe the IA symptoms). Post-baseline raw IA subscale scores are converted to a change from baseline score. A lower change from baseline IA subscale score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 2	-6.1 units on a scale Standard Deviation 5.58
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 4	-7.9 units on a scale Standard Deviation 6.11
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 12	-9.5 units on a scale Standard Deviation 6.26
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 28	-11.2 units on a scale Standard Deviation 5.91
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 36	-11.3 units on a scale Standard Deviation 5.94
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Raw score; Baseline	21.6 units on a scale Standard Deviation 3.39
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 20	-10.2 units on a scale Standard Deviation 6.99
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 44	-10.9 units on a scale Standard Deviation 6.56
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 52	-11.8 units on a scale Standard Deviation 6.00
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 60	-12.5 units on a scale Standard Deviation 6.63
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 68	-11.6 units on a scale Standard Deviation 7.06
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 76	-13.2 units on a scale Standard Deviation 6.31
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 84	-12.2 units on a scale Standard Deviation 6.94
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 92	-13.2 units on a scale Standard Deviation 7.36
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 100	-12.6 units on a scale Standard Deviation 6.89
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 108	-14.1 units on a scale Standard Deviation 7.18
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 116	-14.0 units on a scale Standard Deviation 8.14
Effect of SPN-812 on Inattention (IA) Symptoms as Measured by the Adult ADHD Investigator Symptom Rating IA Subscale Change from baseline score; Week 124	-11.3 units on a scale Standard Deviation 8.54

SECONDARY outcome

Timeframe: Weeks 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, the percent is based on number of "responders" (m) and number of subjects analyzed (n; subjects with a valid AISRS assessment at baseline \[pre-dosing\] and at respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate by visit. The AISRS is an ADHD-specific rating scale designed/validated to assess the 18 symptoms (items) of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Each item is rated on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). The sum of the 18 ratings yields the Total score (range: 0-54; higher score represents severer symptoms). Percent reduction is calculated for each post-baseline AISRS score: \[("Post-baseline" - "Baseline")/"Baseline"\] x 100; range: 0 to 100%; a "responder" is a subject with a 50% or greater reduction in change from baseline Total score. Responder rate (percent of responders) is calculated: \["number of 'responders' (m)" / "number of subjects analyzed" (n)\] X 100; range: 0 to 100%. A Responder Rate greater than 50%, represents more "responders" versus "nonresponders".

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 60	71.8 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 2	22.6 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 4	38.6 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 12	58.0 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 20	55.8 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 28	61.7 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 36	64.2 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 44	64.4 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 52	66.7 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 68	63.9 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 76	78.8 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 84	72.4 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 92	80.0 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 100	69.2 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 108	77.8 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 116	75.0 percentage of subjects
Effect of SPN-812 on the 50% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 124	50.0 percentage of subjects

SECONDARY outcome

Timeframe: Weeks 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, the percent is based on number of "responders" (m) and number of subjects analyzed (n; subjects with a valid AISRS assessment at baseline \[pre-dosing\] and at respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate by visit. The AISRS is an ADHD-specific rating scale designed/validated to assess the 18 symptoms (items) of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Each item is rated on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). The sum of the 18 ratings yields the Total score (range: 0-54; higher score represents severer symptoms). Percent reduction is calculated for each post-baseline AISRS score: \[("Post-baseline" - "Baseline")/"Baseline"\] x 100; range: 0 to 100%; a "responder" is a subject with a 50% or greater reduction in change from baseline Total score. Responder rate (percent of responders) is calculated: \["number of 'responders' (m)" / "number of subjects analyzed" (n)\] X 100; range: 0 to 100%. A Responder Rate greater than 30%, represents more "responders" versus "nonresponders".

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 44	86.4 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 92	92.0 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 2	46.6 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 4	64.4 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 12	72.3 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 20	77.9 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 28	80.2 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 36	83.6 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 52	84.3 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 60	87.2 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 68	91.7 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 76	93.9 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 84	89.7 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 100	92.3 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 108	88.9 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 116	87.5 percentage of subjects
Effect of SPN-812 on the 30% Adult ADHD Investigator Symptom Rating Scale (AISRS) Responder Rate Percent of subjects; Week 124	75.0 percentage of subjects

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Global Executive Composite (GEC) T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning (GEC) and 9 non-overlapping scales among 2 summary index scales (Metacognition Index \[MI\] and Behavioral Regulation Index \[BRI\]) that assess aspects of executive function and problems with self-regulation from the perspective of the individual. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience in past month. The sum of 70 items yields the GEC raw score (range: 70-210), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). Post-baseline GEC T-scores are converted to a change from baseline T-score. A lower change from baseline GEC T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-10.0 T-score Standard Deviation 11.46
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	70.4 T-score Standard Deviation 10.94
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	-1.9 T-score Standard Deviation 8.20
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-9.3 T-score Standard Deviation 9.91
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-13.0 T-score Standard Deviation 12.20
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-14.2 T-score Standard Deviation 12.76
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-14.6 T-score Standard Deviation 12.00
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-14.2 T-score Standard Deviation 11.72
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-15.1 T-score Standard Deviation 13.84
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-15.4 T-score Standard Deviation 14.32
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-16.3 T-score Standard Deviation 15.21
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-16.7 T-score Standard Deviation 15.10
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-15.9 T-score Standard Deviation 12.72
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-14.8 T-score Standard Deviation 15.00
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-16.1 T-score Standard Deviation 16.27
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-17.8 T-score Standard Deviation 20.60
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-12.9 T-score Standard Deviation 17.28
Effect of SPN-812 on Overall Executive Function in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-13.7 T-score Standard Deviation 28.54

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Behavioral Regulation Index (BRI) T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The BRI captures the ability to maintain appropriate regulatory control of one's own behavior and emotional responses. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience in past month. The sum of 30 items yields the BRI raw score (range: 30-90), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). Post-baseline BRI T-scores are converted to a change from baseline T-score. A lower change from baseline BRI T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-8.4 T-score Standard Deviation 9.32
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-10.0 T-score Standard Deviation 24.56
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	63.0 T-score Standard Deviation 11.16
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	-0.5 T-score Standard Deviation 5.92
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-8.7 T-score Standard Deviation 10.66
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-10.6 T-score Standard Deviation 10.70
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-10.7 T-score Standard Deviation 11.59
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-11.7 T-score Standard Deviation 10.86
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-11.0 T-score Standard Deviation 10.61
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-12.3 T-score Standard Deviation 12.88
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-11.6 T-score Standard Deviation 13.09
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-12.8 T-score Standard Deviation 14.04
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-13.1 T-score Standard Deviation 13.43
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-13.1 T-score Standard Deviation 10.66
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-12.0 T-score Standard Deviation 11.82
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-12.8 T-score Standard Deviation 12.10
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-14.8 T-score Standard Deviation 18.40
Effect of SPN-812 on Behavior Regulation in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-12.9 T-score Standard Deviation 15.69

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Metacognition Index (MI) T-score. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. MI reflects individual's ability to problem solve (includes initiate activity, generate ideas, sustain working memory, plan/organize approaches, monitor success/failure, and organize materials/environment). Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience in past month. The sum of 40 items yields the MI raw score (range: 40-120), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). Post-baseline MI T-scores are converted to a change from baseline T-score. A lower change from baseline MI T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	73.4 T-score Standard Deviation 11.56
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	-2.4 T-score Standard Deviation 9.36
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-8.9 T-score Standard Deviation 10.45
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-10.0 T-score Standard Deviation 11.80
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-12.9 T-score Standard Deviation 13.00
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-15.0 T-score Standard Deviation 13.04
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-15.0 T-score Standard Deviation 12.46
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-14.8 T-score Standard Deviation 12.02
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-15.3 T-score Standard Deviation 13.58
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-16.2 T-score Standard Deviation 14.24
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-16.9 T-score Standard Deviation 15.32
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-17.2 T-score Standard Deviation 15.71
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-15.9 T-score Standard Deviation 13.93
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-14.7 T-score Standard Deviation 16.41
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-16.7 T-score Standard Deviation 17.47
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-18.1 T-score Standard Deviation 20.59
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-11.9 T-score Standard Deviation 18.25
Effect of SPN-812 on Metacognition in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-14.7 T-score Standard Deviation 27.30

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) "Inhibit" scale T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The "Inhibit" scale is one of four Behavioral Regulation Index-related scales; it captures the ability to control impulses and appropriately stop verbal, attentional, and physical behavior at the proper time. Subject's rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience in past month. The sum of 8 items yields the "Inhibit" raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). Post-baseline T-scores are converted to a change from baseline (CFB) T-score. A lower CFB "Inhibit" T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	68.8 T-score Standard Deviation 9.83
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	-2.5 T-score Standard Deviation 10.16
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-9.5 T-score Standard Deviation 9.57
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-10.8 T-score Standard Deviation 10.90
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-12.3 T-score Standard Deviation 11.54
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-13.2 T-score Standard Deviation 11.27
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-14.8 T-score Standard Deviation 11.13
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-14.1 T-score Standard Deviation 10.59
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-16.4 T-score Standard Deviation 12.93
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-15.7 T-score Standard Deviation 12.10
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-15.5 T-score Standard Deviation 12.07
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-15.1 T-score Standard Deviation 13.24
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-15.3 T-score Standard Deviation 9.49
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-15.4 T-score Standard Deviation 11.94
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-16.5 T-score Standard Deviation 12.19
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-19.0 T-score Standard Deviation 15.88
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-15.7 T-score Standard Deviation 12.72
Effect of SPN-812 on the "Inhibit" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-12.7 T-score Standard Deviation 22.03

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) "Self-Monitor" scale T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The "Self-Monitor" scale is one of four Behavioral Regulation Index-related scales; it reflects an individual's ability to recognize the effect of their own behavior on others. The subject rates each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience in past month. The sum of 6 items yields the "Self-Monitor" raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). Post-baseline T-scores are converted to a change from baseline (CFB) T-score. A lower CFB "Self-Monitor" T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	60.4 T-score Standard Deviation 12.71
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	-0.7 T-score Standard Deviation 11.64
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-7.8 T-score Standard Deviation 10.14
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-7.2 T-score Standard Deviation 10.15
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-9.5 T-score Standard Deviation 11.00
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-10.3 T-score Standard Deviation 12.72
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-11.3 T-score Standard Deviation 12.89
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-10.9 T-score Standard Deviation 12.39
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-11.3 T-score Standard Deviation 14.97
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-10.1 T-score Standard Deviation 16.32
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-11.6 T-score Standard Deviation 16.62
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-11.3 T-score Standard Deviation 16.61
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-9.9 T-score Standard Deviation 12.32
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-9.0 T-score Standard Deviation 15.01
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-7.5 T-score Standard Deviation 13.49
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-6.6 T-score Standard Deviation 17.26
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-2.9 T-score Standard Deviation 16.48
Effect of SPN-812 on the "Self-Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	1.0 T-score Standard Deviation 15.52

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) "Plan/Organize" scale T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The "Plan/Organize" scale is one of five Metacognition Index-related scales; captures an individual's ability to anticipate events, set goals, pre-plan, organize, and carry out tasks systematically. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience in past month. The sum of 10 items yields the "Plan/Organize" raw score (range: 10-30), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥65 is considered abnormally elevated). Post-baseline T-scores are converted to a change from baseline (CFB) T-score. A lower CFB "Plan/Organize" T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-13.2 T-score Standard Deviation 12.47
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	70.6 T-score Standard Deviation 12.62
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	0.1 T-score Standard Deviation 11.71
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-8.5 T-score Standard Deviation 10.94
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-8.6 T-score Standard Deviation 11.87
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-12.0 T-score Standard Deviation 13.29
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-13.2 T-score Standard Deviation 13.20
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-12.1 T-score Standard Deviation 12.21
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-12.7 T-score Standard Deviation 12.49
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-13.7 T-score Standard Deviation 13.28
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-14.3 T-score Standard Deviation 15.35
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-14.4 T-score Standard Deviation 14.32
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-13.3 T-score Standard Deviation 14.49
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-12.8 T-score Standard Deviation 17.07
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-14.2 T-score Standard Deviation 18.32
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-15.3 T-score Standard Deviation 19.50
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-11.7 T-score Standard Deviation 16.73
Effect of SPN-812 on the "Plan/Organize" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-17.3 T-score Standard Deviation 25.32

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) "Shift" scale T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The "Shift" scale is one of four Behavioral Regulation Index-related scales; it captures one's ability to move freely from one situation/activity/aspect of a problem to another and think flexibly to aid problem-solving. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience in past month. The sum of 6 items yields the "Shift" raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). Post-baseline T-scores are converted to a change from baseline (CFB) T-score. A lower CFB "Shift" T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	63.7 T-score Standard Deviation 12.34
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	-1.9 T-score Standard Deviation 9.41
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-7.3 T-score Standard Deviation 10.65
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-8.2 T-score Standard Deviation 12.22
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-8.9 T-score Standard Deviation 13.26
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-9.4 T-score Standard Deviation 12.54
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-9.7 T-score Standard Deviation 11.30
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-8.6 T-score Standard Deviation 12.31
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-9.0 T-score Standard Deviation 13.40
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-8.5 T-score Standard Deviation 13.23
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-9.6 T-score Standard Deviation 14.08
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-10.7 T-score Standard Deviation 12.35
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-10.4 T-score Standard Deviation 11.63
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-9.1 T-score Standard Deviation 12.37
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-11.5 T-score Standard Deviation 12.43
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-13.7 T-score Standard Deviation 17.28
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-12.1 T-score Standard Deviation 14.88
Effect of SPN-812 on the "Shift" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-13.7 T-score Standard Deviation 30.60

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) "Initiate" scale T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The "Initiate" scale is one of five Metacognition Index-related scales; it captures an individual's ability to begin a task or activity without external prompting and to independently generate ideas. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience in past month. The sum of 8 items yields the "Initiate" scale raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). Post-baseline T-scores are converted to a change from baseline (CFB) T-score. A lower CFB "Initiate" T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-11.6 T-score Standard Deviation 11.89
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	68.0 T-score Standard Deviation 10.83
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	1.9 T-score Standard Deviation 8.59
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-6.2 T-score Standard Deviation 10.68
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-8.0 T-score Standard Deviation 12.01
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-9.8 T-score Standard Deviation 12.96
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-11.7 T-score Standard Deviation 12.53
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-10.7 T-score Standard Deviation 11.25
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-11.7 T-score Standard Deviation 13.64
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-12.1 T-score Standard Deviation 13.16
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-14.4 T-score Standard Deviation 13.61
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-15.9 T-score Standard Deviation 13.81
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-12.7 T-score Standard Deviation 11.31
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-12.0 T-score Standard Deviation 13.09
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-15.0 T-score Standard Deviation 13.23
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-14.0 T-score Standard Deviation 14.21
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-11.9 T-score Standard Deviation 10.76
Effect of SPN-812 on the "Initiate" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-13.7 T-score Standard Deviation 18.48

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) "Task Monitor" scale T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The "Task Monitor" scale is one of five Metacognition Index-related scales; it captures an individual's ability to assess performance for mistakes during or after finishing a task. The subject rates each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience in past month. The sum of 6 items yields the "Task Monitor" raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). Post-baseline T-scores are converted to a change from baseline (CFB) T-score. A lower CFB "Task Monitor" T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	71.1 T-score Standard Deviation 11.67
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	-1.4 T-score Standard Deviation 9.46
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-7.6 T-score Standard Deviation 11.14
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-8.4 T-score Standard Deviation 11.70
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-10.2 T-score Standard Deviation 13.68
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-13.0 T-score Standard Deviation 12.57
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-12.7 T-score Standard Deviation 12.79
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-12.8 T-score Standard Deviation 12.33
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-14.1 T-score Standard Deviation 14.99
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-16.4 T-score Standard Deviation 15.23
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-14.9 T-score Standard Deviation 16.02
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-16.1 T-score Standard Deviation 15.82
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-13.4 T-score Standard Deviation 16.15
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-11.3 T-score Standard Deviation 19.47
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-14.1 T-score Standard Deviation 19.74
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-14.7 T-score Standard Deviation 21.50
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-7.9 T-score Standard Deviation 22.39
Effect of SPN-812 on the "Task Monitor" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-9.3 T-score Standard Deviation 21.83

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) "Emotional Control" scale T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The "Emotional Control" scale is one of four Behavioral Regulation Index-related scales; it captures an individual's ability to modulate their emotional responses appropriately. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience in past month. The sum of 10 items yields the "Emotional Control" raw score (range: 10-30), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). Post-baseline T-scores are converted to a change from baseline (CFB) T-score. A lower CFB "Emotional Control" T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	53.5 T-score Standard Deviation 11.95
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	1.5 T-score Standard Deviation 5.27
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-4.5 T-score Standard Deviation 9.38
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-4.0 T-score Standard Deviation 10.35
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-5.6 T-score Standard Deviation 9.90
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-4.7 T-score Standard Deviation 11.22
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-5.1 T-score Standard Deviation 10.36
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-4.5 T-score Standard Deviation 9.74
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-5.5 T-score Standard Deviation 11.38
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-5.5 T-score Standard Deviation 11.30
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-6.6 T-score Standard Deviation 13.00
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-7.4 T-score Standard Deviation 11.97
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-8.1 T-score Standard Deviation 11.72
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-7.0 T-score Standard Deviation 10.51
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-7.6 T-score Standard Deviation 11.23
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-9.8 T-score Standard Deviation 16.01
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-10.4 T-score Standard Deviation 12.79
Effect of SPN-812 on the "Emotional Control" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-6.7 T-score Standard Deviation 16.50

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) "Working Memory" scale T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The "Working Memory" scale is one of five Metacognition Index-related scales; it captures one's ability to hold information in mind in order to complete a task and stay with, or stick to, an activity. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience in past month. The sum of 8 items yields the "Working Memory" raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥65 is considered abnormally elevated). Post-baseline T-scores are converted to a change from baseline (CFB) T-score. A lower CFB "Working Memory" T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	77.4 T-score Standard Deviation 10.59
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	-6.2 T-score Standard Deviation 11.29
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-9.7 T-score Standard Deviation 11.22
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-11.8 T-score Standard Deviation 12.73
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-14.0 T-score Standard Deviation 13.12
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-15.5 T-score Standard Deviation 13.44
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-15.6 T-score Standard Deviation 12.70
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-17.2 T-score Standard Deviation 11.91
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-16.8 T-score Standard Deviation 14.43
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-17.0 T-score Standard Deviation 14.74
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-16.9 T-score Standard Deviation 15.92
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-17.0 T-score Standard Deviation 15.57
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-18.4 T-score Standard Deviation 13.12
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-17.4 T-score Standard Deviation 14.56
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-15.2 T-score Standard Deviation 18.48
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-18.2 T-score Standard Deviation 20.52
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-7.0 T-score Standard Deviation 18.65
Effect of SPN-812 on the "Working Memory" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-11.0 T-score Standard Deviation 27.22

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid BRIEF-A assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) "Organization of Materials" scale T-score by visit. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The "Organization of Materials" scale is one of five Metacognition Index-related scales; it captures one's ability to keep areas orderly and maintain materials. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience in past month. The sum of 8 items yields the "Organization of Materials" raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). Post-baseline T-scores are converted to a change from baseline (CFB) T-score. A lower CFB "Organization of Materials" T-score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 4	-6.9 T-score Standard Deviation 9.11
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 60	-11.8 T-score Standard Deviation 11.95
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) T-score; Baseline	64.4 T-score Standard Deviation 12.22
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 2	-5.3 T-score Standard Deviation 9.88
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 12	-7.8 T-score Standard Deviation 10.25
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 20	-8.7 T-score Standard Deviation 11.51
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 28	-11.1 T-score Standard Deviation 10.77
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 36	-11.7 T-score Standard Deviation 11.23
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 44	-11.3 T-score Standard Deviation 11.25
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 52	-11.2 T-score Standard Deviation 11.33
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 68	-12.5 T-score Standard Deviation 12.29
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 76	-11.5 T-score Standard Deviation 13.34
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 84	-10.4 T-score Standard Deviation 12.45
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 92	-10.4 T-score Standard Deviation 12.47
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 100	-12.5 T-score Standard Deviation 13.94
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 108	-14.4 T-score Standard Deviation 17.88
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 116	-10.3 T-score Standard Deviation 15.52
Effect of SPN-812 on "Organization of Materials" Scale in Adults With ADHD as Measured by the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A; Self Report) Change from baseline T-score; Week 124	-10.3 T-score Standard Deviation 26.08

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid SDQ assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Symptoms of Depression Questionnaire (SDQ) Total Score by visit. The SDQ is a 44-item self-rating scale assessing overall depression and 5 related symptoms/subscales, including items related to lassitude, mood, and cognitive functioning (18 items; SDQ-1); anxiety, agitation, irritability, and anger (13 items; SDQ-2); suicidal ideation (6 items; SDQ-3); disruptions in sleep quality (3 items; SDQ-4); and changes in appetite and weight (4 items; SDQ-5). Each item is rated on a 6-point scale based on a subject's perception in past month of what is normal (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). The sum of 44 items yields the raw Total score (range: 44-264); a higher Total score indicates worse depression. Post-baseline raw Total scores are converted to a change from baseline score. A lower change from baseline Total score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 28	-3.5 units on a scale Standard Deviation 17.24
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Raw score; Baseline	105.9 units on a scale Standard Deviation 17.18
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 2	4.8 units on a scale Standard Deviation 17.03
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 4	-2.7 units on a scale Standard Deviation 14.57
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 12	-1.9 units on a scale Standard Deviation 19.79
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 20	-3.8 units on a scale Standard Deviation 16.50
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 36	-2.7 units on a scale Standard Deviation 17.15
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 44	-6.2 units on a scale Standard Deviation 16.56
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 52	-4.0 units on a scale Standard Deviation 19.22
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 60	-5.3 units on a scale Standard Deviation 15.63
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 68	-5.9 units on a scale Standard Deviation 20.64
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 76	-8.2 units on a scale Standard Deviation 15.11
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 84	-7.1 units on a scale Standard Deviation 12.49
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 92	-8.4 units on a scale Standard Deviation 12.83
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 100	-6.4 units on a scale Standard Deviation 11.61
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 108	-2.9 units on a scale Standard Deviation 20.37
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 116	-3.6 units on a scale Standard Deviation 18.19
Effect of SPN-812 on Overall Symptoms of Depression in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 124	-9.0 units on a scale Standard Deviation 13.74

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid SDQ assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Symptoms of Depression Questionnaire (SDQ) "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale Score by visit. The SDQ is a 44-item self-rating scale assessing overall depression and 5 related symptoms/subscales, including 18 items related to lassitude, mood, and cognitive functioning (SDQ-1 subscale). Each item is rated on a 6-point scale based on a subject's perception in past month of what is normal (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). The sum of these 18 items yields the raw SDQ-1 subscale score (range: 17-102); a higher SDQ-1 subscale score indicates worse lassitude, mood, and cognitive functioning. Post-baseline raw SDQ-1 subscale scores are converted to a change from baseline score. A lower change from baseline SDQ-1 subscale score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 4	-2.4 units on a scale Standard Deviation 7.94
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 12	-2.3 units on a scale Standard Deviation 10.70
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 44	-4.0 units on a scale Standard Deviation 10.14
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 76	-5.4 units on a scale Standard Deviation 10.31
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 124	-5.8 units on a scale Standard Deviation 8.02
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Raw score; Baseline	45.6 units on a scale Standard Deviation 9.40
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 2	0.5 units on a scale Standard Deviation 9.55
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 20	-3.0 units on a scale Standard Deviation 9.95
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 28	-3.2 units on a scale Standard Deviation 10.28
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 36	-2.7 units on a scale Standard Deviation 9.99
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 52	-3.3 units on a scale Standard Deviation 11.01
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 60	-4.2 units on a scale Standard Deviation 10.64
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 68	-3.9 units on a scale Standard Deviation 12.79
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 84	-3.9 units on a scale Standard Deviation 6.46
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 92	-3.8 units on a scale Standard Deviation 7.74
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 100	-2.6 units on a scale Standard Deviation 6.37
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 108	-2.1 units on a scale Standard Deviation 9.55
Effect of SPN-812 on "Lassitude, Mood, and Cognitive Functioning" (SDQ-1) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 116	-1.7 units on a scale Standard Deviation 8.50

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid SDQ assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Symptoms of Depression Questionnaire (SDQ) "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Score by visit. The SDQ is a 44-item self-rating scale assessing overall depression and 5 related symptoms/subscales, including 13 items related to anxiety, agitation, irritability, and anger (SDQ-2 subscale). Each item is rated on a 6-point scale based on a subject's perception in past month of what is normal (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). The sum of these 13 items yields the raw SDQ-2 subscale score (range: 13-78); a higher SDQ-2 subscale score indicates worse anxiety, agitation, irritability, and anger. Post-baseline raw SDQ-2 subscale scores are converted to a change from baseline score. A lower change from baseline SDQ-2 subscale score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 4	-0.6 units on a scale Standard Deviation 5.49
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 12	0.0 units on a scale Standard Deviation 6.97
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 76	-1.8 units on a scale Standard Deviation 4.32
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Raw score; Baseline	31.1 units on a scale Standard Deviation 5.93
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 2	2.6 units on a scale Standard Deviation 4.86
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 20	-0.6 units on a scale Standard Deviation 5.70
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 28	-0.6 units on a scale Standard Deviation 5.79
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 36	0.0 units on a scale Standard Deviation 6.07
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 44	-1.4 units on a scale Standard Deviation 5.18
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 52	-0.7 units on a scale Standard Deviation 5.23
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 60	-0.9 units on a scale Standard Deviation 4.66
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 68	-0.8 units on a scale Standard Deviation 5.96
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 84	-1.2 units on a scale Standard Deviation 4.87
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 92	-2.9 units on a scale Standard Deviation 4.59
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 100	-2.3 units on a scale Standard Deviation 3.88
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 108	0.1 units on a scale Standard Deviation 6.62
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 116	-0.4 units on a scale Standard Deviation 5.29
Effect of SPN-812 on "Anxiety, Agitation, Irritability, and Anger" (SDQ-2) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 124	-1.0 units on a scale Standard Deviation 4.55

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid SDQ assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Symptoms of Depression Questionnaire (SDQ) "Suicidal Ideation" (SDQ-3) Subscale by visit. The SDQ is a 44-item self-rating scale assessing overall depression and 5 related symptoms/subscales, including 6 items related to suicidal ideation (SDQ-3). Each item is rated on a 6-point scale based on a subject's perception in past month of what is normal (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). The sum of these 6 items yields the raw SDQ-3 subscale score (range: 6-36); a higher SDQ-3 subscale score indicates worse "suicidal ideation". Post-baseline raw SDQ-3 subscale scores are converted to a change from baseline score. A lower change from baseline SDQ-3 subscale score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 124	-0.8 units on a scale Standard Deviation 1.26
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Raw score; Baseline	12.4 units on a scale Standard Deviation 1.92
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 2	0.3 units on a scale Standard Deviation 2.61
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 4	-0.1 units on a scale Standard Deviation 2.06
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 12	-0.1 units on a scale Standard Deviation 2.53
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 20	0.0 units on a scale Standard Deviation 2.31
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 28	0.1 units on a scale Standard Deviation 2.08
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 36	0.3 units on a scale Standard Deviation 2.63
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 44	-0.1 units on a scale Standard Deviation 2.13
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 52	0.4 units on a scale Standard Deviation 2.80
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 60	0.0 units on a scale Standard Deviation 1.99
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 68	-0.2 units on a scale Standard Deviation 2.19
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 76	-0.3 units on a scale Standard Deviation 1.90
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 84	-0.3 units on a scale Standard Deviation 1.79
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 92	-0.5 units on a scale Standard Deviation 1.39
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 100	-0.8 units on a scale Standard Deviation 1.42
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 108	0.3 units on a scale Standard Deviation 1.73
Effect of SPN-812 on "Suicidal Ideation" (SDQ-3) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 116	-0.3 units on a scale Standard Deviation 1.89

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid SDQ assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Symptoms of Depression Questionnaire (SDQ) "Disruptions in Sleep Quality" (SDQ-4) Subscale Score by visit. The SDQ is a 44-item self-rating scale assessing overall depression and 5 related symptoms/subscales, including 3 items related to disruptions in sleep quality (SDQ-4). Each item is rated on a 6-point scale based on a subject's perception in past month of what is normal (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). The sum of these 3 items yields the raw SDQ-4 subscale score (range: 3-18); a higher SDQ-4 subscale score indicates worse disruptions in sleep quality. Post-baseline raw SDQ-4 subscale scores are converted to a change from baseline score. A lower change from baseline SDQ-4 subscale score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 28	0.0 units on a scale Standard Deviation 2.15
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Raw score; Baseline	7.9 units on a scale Standard Deviation 2.38
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 2	1.1 units on a scale Standard Deviation 3.75
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 4	0.1 units on a scale Standard Deviation 2.93
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 12	0.1 units on a scale Standard Deviation 3.14
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 20	-0.2 units on a scale Standard Deviation 2.45
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 36	-0.3 units on a scale Standard Deviation 2.20
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 44	-0.6 units on a scale Standard Deviation 2.42
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 52	-0.6 units on a scale Standard Deviation 2.97
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 60	-0.5 units on a scale Standard Deviation 3.02
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 68	-1.2 units on a scale Standard Deviation 2.68
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 76	-0.7 units on a scale Standard Deviation 2.61
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 84	-1.6 units on a scale Standard Deviation 2.21
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 92	-1.4 units on a scale Standard Deviation 2.86
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 100	-0.2 units on a scale Standard Deviation 3.08
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 108	-1.0 units on a scale Standard Deviation 3.54
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 116	-0.9 units on a scale Standard Deviation 4.38
Effect of SPN-812 on "Disruptions in Sleep Quality" (SDQ-4) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 124	-1.8 units on a scale Standard Deviation 2.75

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid SDQ assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Symptoms of Depression Questionnaire (SDQ) "Appetite and Weight" (SDQ-5) Subscale Score by visit. The SDQ is a 44-item self-rating scale assessing overall depression and 5 related symptoms/subscales, including 4 items related to changes in appetite and weight (SDQ-5). Each item is rated on a 6-point scale based on a subject's perception in past month of what is normal (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). The sum of these 4 items yields the raw SDQ-5 subscale score (range: 4-24); a higher SDQ-5 subscale score indicates worse appetite and weight. Post-baseline raw SDQ-5 subscale scores are converted to a change from baseline score. A lower change from baseline SDQ-5 subscale score (\<0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 100	-0.5 units on a scale Standard Deviation 0.78
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 60	0.4 units on a scale Standard Deviation 1.39
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 68	0.2 units on a scale Standard Deviation 1.57
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Raw score; Baseline	8.9 units on a scale Standard Deviation 1.32
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 2	0.4 units on a scale Standard Deviation 0.93
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 4	0.2 units on a scale Standard Deviation 1.47
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 12	0.4 units on a scale Standard Deviation 1.48
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 20	0.2 units on a scale Standard Deviation 1.51
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 28	0.1 units on a scale Standard Deviation 1.62
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 36	0.1 units on a scale Standard Deviation 1.89
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 44	0.0 units on a scale Standard Deviation 1.40
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 52	0.1 units on a scale Standard Deviation 1.55
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 76	0.1 units on a scale Standard Deviation 1.20
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 84	0.0 units on a scale Standard Deviation 1.09
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 92	0.2 units on a scale Standard Deviation 1.46
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 108	-0.2 units on a scale Standard Deviation 1.39
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 116	-0.3 units on a scale Standard Deviation 1.50
Effect of SPN-812 on "Appetite and Weight" (SDQ-5) Subscale in Adults With ADHD as Measured by the Symptoms of Depression Questionnaire (SDQ) Change from baseline score; Week 124	0.3 units on a scale Standard Deviation 1.26

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid AAQoL assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Adult ADHD Quality of Life Scale (AAQoL) Total score by visit. The AAQoL is a 29-item self-rating scale assessing how ADHD has impacted his/her quality of life. It includes 4 related aspects (subscales) of quality of life, including Life Productivity (11 items), Psychological Health (6 items), Relationships (5 items), and Life Outlook (7 items). Each item is rated on a 5-point scale based on a subject's perception in past 2 weeks, where 1 = Not at all/Never, 2 = A little, 3 = Somewhat, 4 = A lot, and 5 = Extremely/Very often. Item scores are transformed to a 0 to 100-point scale (1=0; 2=5; 3=50; 4=75; 5=100). The sum of the transformed 29 items is divided by 29 to yield the raw Total score (range: 0-100); a higher raw Total score represents better quality of life. Post-baseline raw Total scores are converted to a change from baseline (CFB) Total score. A higher CFB Total score (\>0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 44	17.7 units on a scale Standard Deviation 15.76
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Raw score; Baseline	54.9 units on a scale Standard Deviation 14.96
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 2	4.5 units on a scale Standard Deviation 10.08
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 4	10.3 units on a scale Standard Deviation 14.66
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 12	12.2 units on a scale Standard Deviation 17.18
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 20	13.6 units on a scale Standard Deviation 18.89
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 28	16.6 units on a scale Standard Deviation 17.76
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 36	14.7 units on a scale Standard Deviation 17.91
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 52	16.7 units on a scale Standard Deviation 17.08
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 60	16.6 units on a scale Standard Deviation 16.96
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 68	16.7 units on a scale Standard Deviation 18.09
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 76	17.2 units on a scale Standard Deviation 14.68
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 84	17.3 units on a scale Standard Deviation 14.83
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 92	18.2 units on a scale Standard Deviation 17.11
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 100	14.5 units on a scale Standard Deviation 14.47
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 108	15.8 units on a scale Standard Deviation 17.28
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 116	14.5 units on a scale Standard Deviation 16.14
Effect of SPN-812 on Overall Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 124	6.0 units on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid AAQoL assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Adult ADHD Quality of Life Scale (AAQoL) "Life Productivity" subscale score by visit. The AAQoL is a 29-item self-rating scale assessing how ADHD has impacted his/her quality of life, which includes 11 items related to Life Productivity. Each item is rated on a 5-point scale based on a subject's perception in past 2 weeks, where 1 = Not at all/Never, 2 = A little, 3 = Somewhat, 4 = A lot, and 5 = Extremely/Very often. Item scores are transformed to a 0 to 100-point scale (1=0; 2=5; 3=50; 4=75; 5=100). The sum of the transformed 11 items is divided by 11 to yield the raw "Life Productivity" subscale score (range: 0-100); the higher the "Life Productivity" subscale score, the better Life Productivity. Post-baseline raw "Life Productivity" subscale scores are converted to a change from baseline score. A higher change from baseline "Life Productivity" subscale score (\>0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 2	13.6 units on a scale Standard Deviation 17.19
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Raw score; Baseline	45.6 units on a scale Standard Deviation 21.27
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 4	18.0 units on a scale Standard Deviation 19.79
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 12	18.9 units on a scale Standard Deviation 22.07
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 20	21.3 units on a scale Standard Deviation 26.26
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 28	24.4 units on a scale Standard Deviation 23.91
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 36	23.5 units on a scale Standard Deviation 25.21
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 44	24.1 units on a scale Standard Deviation 22.86
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 52	25.8 units on a scale Standard Deviation 24.38
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 60	26.9 units on a scale Standard Deviation 25.13
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 68	26.5 units on a scale Standard Deviation 22.23
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 76	26.2 units on a scale Standard Deviation 23.41
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 84	27.2 units on a scale Standard Deviation 20.98
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 92	26.5 units on a scale Standard Deviation 23.20
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 100	25.5 units on a scale Standard Deviation 24.00
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 108	32.1 units on a scale Standard Deviation 26.07
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 116	30.2 units on a scale Standard Deviation 26.88
Effects of SPN-812 on "Life Productivity" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 124	39.4 units on a scale Standard Deviation 27.11

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid AAQoL assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Adult ADHD Quality of Life Scale (AAQoL) "Psychological Health" subscale score by visit. The AAQoL is a 29-item self-rating scale assessing how ADHD has impacted his/her quality of life, which includes 6 items related to Psychological Health. Each item is rated on a 5-point scale based on a subject's perception in past 2 weeks, where 1 = Not at all/Never, 2 = A little, 3 = Somewhat, 4 = A lot, and 5 = Extremely/Very often. Item scores are transformed to a 0 to 100-point scale (1=0; 2=5; 3=50; 4=75; 5=100). The sum of the transformed 6 items is divided by 6 to yield the raw "Psychological Health" subscale score (range: 0-100); the higher the subscale score, the better Psychological Health. Post-baseline raw "Psychological Health" subscale scores are converted to a change from baseline score. A higher change from baseline "Psychological Health" subscale score (\>0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 84	14.1 units on a scale Standard Deviation 16.72
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Raw score; Baseline	65.1 units on a scale Standard Deviation 19.54
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 2	3.0 units on a scale Standard Deviation 15.63
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 4	5.2 units on a scale Standard Deviation 18.45
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 12	5.6 units on a scale Standard Deviation 21.38
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 20	8.1 units on a scale Standard Deviation 17.97
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 28	9.3 units on a scale Standard Deviation 20.49
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 36	8.6 units on a scale Standard Deviation 18.47
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 44	10.1 units on a scale Standard Deviation 19.17
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 52	7.2 units on a scale Standard Deviation 19.47
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 60	9.5 units on a scale Standard Deviation 17.78
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 68	8.6 units on a scale Standard Deviation 20.51
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 76	13.3 units on a scale Standard Deviation 18.29
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 92	16.0 units on a scale Standard Deviation 18.33
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 100	13.5 units on a scale Standard Deviation 17.36
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 108	15.3 units on a scale Standard Deviation 22.92
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 116	16.1 units on a scale Standard Deviation 17.42
Effects of SPN-812 on "Psychological Health" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 124	22.9 units on a scale Standard Deviation 21.11

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid AAQoL assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Adult ADHD Quality of Life Scale (AAQoL) "Life Outlook" subscale score by visit. The AAQoL is a 29-item self-rating scale assessing how ADHD has impacted his/her quality of life, which includes 7 items related to Life Outlook. Each item is rated on a 5-point scale based on a subject's perception in past 2 weeks, where 1 = Not at all/Never, 2 = A little, 3 = Somewhat, 4 = A lot, and 5 = Extremely/Very often. Item scores are transformed to a 0 to 100-point scale (1=0; 2=5; 3=50; 4=75; 5=100). The sum of the transformed 7 items is divided by 7 to yield the raw "Life Outlook" subscale score (range: 0-100); the higher the subscale score, the better Life Outlook. Post-baseline raw "Life Outlook" subscale scores are converted to a change from baseline score. A higher change from baseline "Life Outlook" subscale score (\>0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Raw score; Baseline	56.0 units on a scale Standard Deviation 14.52
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 2	-3.9 units on a scale Standard Deviation 16.63
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 4	3.1 units on a scale Standard Deviation 16.05
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 12	6.7 units on a scale Standard Deviation 17.18
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 20	7.0 units on a scale Standard Deviation 20.82
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 28	8.8 units on a scale Standard Deviation 21.02
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 36	5.6 units on a scale Standard Deviation 20.79
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 44	10.1 units on a scale Standard Deviation 18.37
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 52	8.6 units on a scale Standard Deviation 18.76
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 60	9.6 units on a scale Standard Deviation 22.77
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 68	12.2 units on a scale Standard Deviation 23.61
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 76	11.8 units on a scale Standard Deviation 13.28
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 84	9.1 units on a scale Standard Deviation 14.90
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 92	10.3 units on a scale Standard Deviation 12.90
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 100	14.3 units on a scale Standard Deviation 17.03
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 108	9.5 units on a scale Standard Deviation 16.39
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 116	7.1 units on a scale Standard Deviation 12.11
Effects of SPN-812 on "Life Outlook" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 124	-1.8 units on a scale Standard Deviation 17.68

SECONDARY outcome

Timeframe: Baseline and Week 2, 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 108, 116, and 124

Population: Safety Population (N), defined as subjects who signed Informed Consent and took at least 1 dose of SPN-812. At each Visit/Week, data is summarized with descriptive statistics for the number of subjects analyzed (n; subjects with a valid AAQoL assessment at baseline \[pre-dosing\] and at the respective post-baseline \[after first dose\] Visit/Week). Due to attrition and/or missing data, the number of subjects analyzed at each Visit/Week may be less than and unequal to Safety Population.

An additional secondary endpoint was the change from baseline in the Adult ADHD Quality of Life Scale (AAQoL) "Relationships" subscale score by visit. The AAQoL is a 29-item self-rating scale assessing how ADHD has impacted his/her quality of life, which includes 5 items related to Relationships. Each item is rated on a 5-point scale based on a subject's perception in past 2 weeks, where 1 = Not at all/Never, 2 = A little, 3 = Somewhat, 4 = A lot, and 5 = Extremely/Very often. Item scores are transformed to a 0 to 100-point scale (1=0; 2=5; 3=50; 4=75; 5=100). The sum of the transformed 5 items is divided by 5 to yield the raw "Relationships" subscale score (range: 0-100); the higher the subscale score, the better the Relationships. Post-baseline raw "Relationships" subscale scores are converted to a change from baseline score. A higher change from baseline "Relationships" subscale score (\>0) represents a better outcome.

Outcome measures

Outcome measures
Measure	Open-Label Treatment n=159 Participants SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Raw score; Baseline	64.7 units on a scale Standard Deviation 19.78
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 2	6.9 units on a scale Standard Deviation 18.09
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 4	6.7 units on a scale Standard Deviation 19.29
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 12	7.2 units on a scale Standard Deviation 21.57
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 20	10.8 units on a scale Standard Deviation 20.34
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 28	10.7 units on a scale Standard Deviation 19.93
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 36	10.1 units on a scale Standard Deviation 22.27
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 44	10.7 units on a scale Standard Deviation 20.36
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 52	13.3 units on a scale Standard Deviation 19.73
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 60	11.8 units on a scale Standard Deviation 19.26
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 68	11.9 units on a scale Standard Deviation 20.37
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 76	14.4 units on a scale Standard Deviation 20.63
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 84	12.7 units on a scale Standard Deviation 21.58
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 92	11.7 units on a scale Standard Deviation 19.26
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 100	13.8 units on a scale Standard Deviation 17.47
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 108	11.9 units on a scale Standard Deviation 18.11
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 116	5.7 units on a scale Standard Deviation 12.05
Effects of SPN-812 on "Relationships" Aspect of Quality of Life in Adults With ADHD as Measured by the Adult ADHD Quality of Life Scale (AAQoL) Change from baseline score; Week 124	18.8 units on a scale Standard Deviation 24.28

Adverse Events

Open-Label Treatment

Serious events: 2 serious events

Other events: 114 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Open-Label Treatment n=159 participants at risk SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Injury, poisoning and procedural complications Fall	0.63% 1/159 • Number of events 1 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
Nervous system disorders Syncope	0.63% 1/159 • Number of events 1 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
Injury, poisoning and procedural complications Spinal column injury	0.63% 1/159 • Number of events 1 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.63% 1/159 • Number of events 1 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
Vascular disorders Deep vein thrombosis	0.63% 1/159 • Number of events 1 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)

Other adverse events

Other adverse events
Measure	Open-Label Treatment n=159 participants at risk SPN-812 Open-Label Treatment 200mg to 600mg SPN-812 once daily for up to 156 weeks SPN-812: SPN-812 200 to 600 mg/day
Psychiatric disorders Insomnia	13.8% 22/159 • Number of events 26 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
Gastrointestinal disorders Nausea	13.8% 22/159 • Number of events 27 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
Nervous system disorders Headache	10.7% 17/159 • Number of events 23 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
General disorders Fatigue	10.1% 16/159 • Number of events 19 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
Infections and infestations Corona virus infection	6.9% 11/159 • Number of events 12 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
Psychiatric disorders Anxiety	6.3% 10/159 • Number of events 10 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
Gastrointestinal disorders Dry mouth	5.0% 8/159 • Number of events 9 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)
Gastrointestinal disorders Vomiting	5.0% 8/159 • Number of events 9 • up to 156 weeks Number of subjects is based on Safety Population (defined as subjects who took at least one dose of SPN-812)

Additional Information

Jonathan Rubin, MD, MBA, Senior Vice President/Chief Medical Officer

Supernus Pharmaceuticals Inc.

Phone: 240-403-5710

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place