Trial Outcomes & Findings for Efficacy and Safety of SPN-812 (Viloxazine Extended-release Capsule) in Children With ADHD (NCT NCT02633527)

Last Updated: 2021-10-27

Results Overview

The Primary Endpoint was the change from baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) Total score at Week 8 (End of Study). The ADHD-RS-IV is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology. The scale consists of 18 items that directly correspond to the 18 Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) symptoms of ADHD. Each item is rated on a 4-point Likert-type scale from 0 (never or rarely) to 3 (very often). A Total score is calculated by adding the responses of all 18 items (range: 0-54; the higher the score, the more severe the ADHD symptoms). Lower change from baseline scores (\<0) represent a better outcome.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

222 participants

Primary outcome timeframe

Baseline to Week 8 (End of Study)

Results posted on

2021-10-27

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Treatment A: Placebo was administered once daily	100mg SPN-812 Treatment B: 100mg SPN-812 was administered once daily and compared to placebo	200mg SPN-812 Treatment C: 200mg SPN-812 was administered once daily and compared to placebo	300mg SPN-812 Treatment D: 300mg SPN-812 was administered once daily and compared to placebo	400mg SPN-812 Treatment E: 400mg SPN-812 was administered once daily and compared to placebo
Overall Study STARTED	24	48	50	49	51
Overall Study COMPLETED	21	37	33	35	34
Overall Study NOT COMPLETED	3	11	17	14	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Treatment A: Placebo was administered once daily	100mg SPN-812 Treatment B: 100mg SPN-812 was administered once daily and compared to placebo	200mg SPN-812 Treatment C: 200mg SPN-812 was administered once daily and compared to placebo	300mg SPN-812 Treatment D: 300mg SPN-812 was administered once daily and compared to placebo	400mg SPN-812 Treatment E: 400mg SPN-812 was administered once daily and compared to placebo
Overall Study Failed to meet eligibility	0	1	1	0	1
Overall Study Adverse Event	0	4	3	1	5
Overall Study Lost to Follow-up	1	2	5	5	4
Overall Study Withdrawal by Subject	0	3	5	4	4
Overall Study Protocol Violation	0	1	1	1	1
Overall Study Physician Decision	0	0	0	0	1
Overall Study Administrative reason	1	0	0	1	0
Overall Study Multiple reasons	1	0	2	2	1

Baseline Characteristics

Efficacy and Safety of SPN-812 (Viloxazine Extended-release Capsule) in Children With ADHD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=24 Participants Treatment A: Placebo was administered once daily	100mg SPN-812 n=45 Participants Treatment B: 100mg SPN-812 was administered once daily and compared to placebo	200mg SPN-812 n=46 Participants Treatment C: 200mg SPN-812 was administered once daily and compared to placebo	300mg SPN-812 n=47 Participants Treatment D: 300mg SPN-812 was administered once daily and compared to placebo	400mg SPN-812 n=44 Participants Treatment E: 400mg SPN-812 was administered once daily and compared to placebo	Total n=206 Participants Total of all reporting groups
Age, Continuous	8.4 years STANDARD_DEVIATION 1.89 • n=5 Participants	8.2 years STANDARD_DEVIATION 1.78 • n=7 Participants	9.1 years STANDARD_DEVIATION 1.95 • n=5 Participants	8.9 years STANDARD_DEVIATION 1.95 • n=4 Participants	9.0 years STANDARD_DEVIATION 2.18 • n=21 Participants	8.8 years STANDARD_DEVIATION 1.97 • n=10 Participants
Age, Customized 6 to 9 years	16 Participants n=5 Participants	36 Participants n=7 Participants	26 Participants n=5 Participants	30 Participants n=4 Participants	27 Participants n=21 Participants	135 Participants n=10 Participants
Age, Customized 10 to 12 years	8 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants	17 Participants n=4 Participants	17 Participants n=21 Participants	71 Participants n=10 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	18 Participants n=7 Participants	13 Participants n=5 Participants	11 Participants n=4 Participants	13 Participants n=21 Participants	68 Participants n=10 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	27 Participants n=7 Participants	33 Participants n=5 Participants	36 Participants n=4 Participants	31 Participants n=21 Participants	138 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	19 Participants n=7 Participants	16 Participants n=5 Participants	22 Participants n=4 Participants	15 Participants n=21 Participants	79 Participants n=10 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	22 Participants n=7 Participants	26 Participants n=5 Participants	24 Participants n=4 Participants	28 Participants n=21 Participants	117 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	6 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Region of Enrollment United States	24 participants n=5 Participants	45 participants n=7 Participants	46 participants n=5 Participants	47 participants n=4 Participants	44 participants n=21 Participants	206 participants n=10 Participants
ADHD RS-IV Total Score	42.4 scores on a scale STANDARD_DEVIATION 7.76 • n=5 Participants	42.4 scores on a scale STANDARD_DEVIATION 6.82 • n=7 Participants	43.9 scores on a scale STANDARD_DEVIATION 7.45 • n=5 Participants	41.3 scores on a scale STANDARD_DEVIATION 7.94 • n=4 Participants	40.8 scores on a scale STANDARD_DEVIATION 7.87 • n=21 Participants	42.1 scores on a scale STANDARD_DEVIATION 7.57 • n=10 Participants
ADHD RS-IV Inattention Subscale Score	21.9 scores on a scale STANDARD_DEVIATION 4.72 • n=5 Participants	22.1 scores on a scale STANDARD_DEVIATION 3.86 • n=7 Participants	22.2 scores on a scale STANDARD_DEVIATION 3.57 • n=5 Participants	21.8 scores on a scale STANDARD_DEVIATION 3.75 • n=4 Participants	21.0 scores on a scale STANDARD_DEVIATION 4.71 • n=21 Participants	21.8 scores on a scale STANDARD_DEVIATION 4.06 • n=10 Participants
ADHD RS-IV Hyperactivity/ Impulsivity Subscale Score	20.5 scores on a scale STANDARD_DEVIATION 4.40 • n=5 Participants	20.3 scores on a scale STANDARD_DEVIATION 5.15 • n=7 Participants	21.7 scores on a scale STANDARD_DEVIATION 5.10 • n=5 Participants	19.4 scores on a scale STANDARD_DEVIATION 5.99 • n=4 Participants	19.7 scores on a scale STANDARD_DEVIATION 4.43 • n=21 Participants	20.3 scores on a scale STANDARD_DEVIATION 5.14 • n=10 Participants

PRIMARY outcome

Timeframe: Baseline to Week 8 (End of Study)

Population: Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) assessment and have at least one post-baseline ADHD-RS-IV assessment

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Treatment A: Placebo was administered once daily	100mg SPN-812 n=45 Participants Treatment B: 100mg SPN-812 was administered once daily and compared to placebo	200mg SPN-812 n=46 Participants Treatment C: 200mg SPN-812 was administered once daily and compared to placebo	300mg SPN-812 n=47 Participants Treatment D: 300mg SPN-812 was administered once daily and compared to placebo	400mg SPN-812 n=44 Participants Treatment E: 400mg SPN-812 was administered once daily and compared to placebo
The Efficacy of SPN-812 on the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV)	-10.5 units on a scale Standard Deviation 11.82	-16.7 units on a scale Standard Deviation 14.57	-18.4 units on a scale Standard Deviation 15.61	-18.6 units on a scale Standard Deviation 14.38	-19.0 units on a scale Standard Deviation 14.51

SECONDARY outcome

Timeframe: Week 8 (End of Study)

The first additional secondary endpoint was the Clinical Global Impression-Improvement (CGI-I) Scale score at Week 8 (End of Study). The CGI-I scale is a single item assessment of how much the patient's illness has improved or worsened relative to a baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point Likert 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". Successful therapy is indicated by a lower score (\<4) in subsequent testing.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Treatment A: Placebo was administered once daily	100mg SPN-812 n=45 Participants Treatment B: 100mg SPN-812 was administered once daily and compared to placebo	200mg SPN-812 n=46 Participants Treatment C: 200mg SPN-812 was administered once daily and compared to placebo	300mg SPN-812 n=47 Participants Treatment D: 300mg SPN-812 was administered once daily and compared to placebo	400mg SPN-812 n=44 Participants Treatment E: 400mg SPN-812 was administered once daily and compared to placebo
Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Scale	3.0 units on a scale Standard Deviation 0.88	2.6 units on a scale Standard Deviation 1.10	2.6 units on a scale Standard Deviation 1.26	2.2 units on a scale Standard Deviation 1.25	2.4 units on a scale Standard Deviation 1.13

SECONDARY outcome

Timeframe: Baseline to Week 8 (End of Study)

The second additional secondary endpoint was the change from baseline in the Clinical Global Impression-Severity (CGI-S) Scale score at Week 8 (End of Study). The CGI-S scale is a single item clinician/investigator rating of the clinician's assessment of the severity of the ADHD symptoms in relation to the clinician's total experience with patients with ADHD. The CGI-S was rated on a 7-point Likert scale, where 1 = Normal, not at all ill, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Extremely Ill. Successful therapy is indicated by a lower CGI-S score in subsequent testing. A lower change from baseline score (\<0) represents a better outcome.