Trial Outcomes & Findings for Evaluation of SPN-812 (Viloxazine Extended-release Capsule) High Dose in Children With ADHD (NCT NCT03247543)
NCT ID: NCT03247543
Last Updated: 2021-07-08
Results Overview
The Primary Endpoint was the change from baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Total score at Week 8 (End of Study). The ADHD-RS-5 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, 5th Edition (DSM-5) symptoms of ADHD. Each item is rated on a 4-point Likert-type scale from 0 (none) to 3 (severe). 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.
COMPLETED
PHASE3
313 participants
Baseline and Week 8 (End of Study)
2021-07-08
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily
|
400mg SPN-812
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily
|
|---|---|---|---|
|
Overall Study
STARTED
|
102
|
107
|
101
|
|
Overall Study
COMPLETED
|
85
|
88
|
78
|
|
Overall Study
NOT COMPLETED
|
17
|
19
|
23
|
Reasons for withdrawal
| Measure |
Placebo
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily
|
400mg SPN-812
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
6
|
4
|
|
Overall Study
Lost to Follow-up
|
10
|
7
|
8
|
|
Overall Study
Consent withdrawn by caregiver
|
2
|
2
|
9
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
|
Overall Study
Failure to Follow study procedures
|
1
|
3
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
0
|
|
Overall Study
Non-compliance with study visits
|
0
|
1
|
0
|
Baseline Characteristics
The sum of each categorical age group is equal to the number of participants in the analysis population.
Baseline characteristics by cohort
| Measure |
Placebo
n=97 Participants
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 Participants
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily
|
400mg SPN-812
n=97 Participants
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily
|
Total
n=301 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
8.5 years
STANDARD_DEVIATION 1.69 • n=5 Participants
|
8.5 years
STANDARD_DEVIATION 1.71 • n=7 Participants
|
8.4 years
STANDARD_DEVIATION 1.66 • n=5 Participants
|
8.4 years
STANDARD_DEVIATION 1.68 • n=4 Participants
|
|
Age, Customized
Age 6 to 9
|
64 Participants
n=5 Participants • The sum of each categorical age group is equal to the number of participants in the analysis population.
|
71 Participants
n=7 Participants • The sum of each categorical age group is equal to the number of participants in the analysis population.
|
68 Participants
n=5 Participants • The sum of each categorical age group is equal to the number of participants in the analysis population.
|
203 Participants
n=4 Participants • The sum of each categorical age group is equal to the number of participants in the analysis population.
|
|
Age, Customized
Age 10 to 11
|
33 Participants
n=5 Participants • The sum of each categorical age group is equal to the number of participants in the analysis population.
|
36 Participants
n=7 Participants • The sum of each categorical age group is equal to the number of participants in the analysis population.
|
29 Participants
n=5 Participants • The sum of each categorical age group is equal to the number of participants in the analysis population.
|
98 Participants
n=4 Participants • The sum of each categorical age group is equal to the number of participants in the analysis population.
|
|
Sex: Female, Male
Female
|
36 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
107 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
61 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
194 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
30 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
91 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
67 Participants
n=5 Participants
|
80 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
210 Participants
n=4 Participants
|
|
Ethnicity (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
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 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
|
|
Race (NIH/OMB)
Black or African American
|
37 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
125 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
53 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
159 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
13 Participants
n=4 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
|
|
Region of Enrollment
United States
|
97 participants
n=5 Participants
|
107 participants
n=7 Participants
|
97 participants
n=5 Participants
|
301 participants
n=4 Participants
|
|
ADHD-RS-5 Total Score
|
43.5 scores on a scale
STANDARD_DEVIATION 6.79 • n=5 Participants
|
43.8 scores on a scale
STANDARD_DEVIATION 6.54 • n=7 Participants
|
45.0 scores on a scale
STANDARD_DEVIATION 6.55 • n=5 Participants
|
44.1 scores on a scale
STANDARD_DEVIATION 6.63 • n=4 Participants
|
|
ADHD-RS-5 Inattention Score
|
22.5 scores on a scale
STANDARD_DEVIATION 3.20 • n=5 Participants
|
22.6 scores on a scale
STANDARD_DEVIATION 3.42 • n=7 Participants
|
23.0 scores on a scale
STANDARD_DEVIATION 3.21 • n=5 Participants
|
22.7 scores on a scale
STANDARD_DEVIATION 3.28 • n=4 Participants
|
|
ADHD-RS-5 Hyperactivity/Impulsivity Score
|
21.0 scores on a scale
STANDARD_DEVIATION 4.78 • n=5 Participants
|
21.2 scores on a scale
STANDARD_DEVIATION 4.54 • n=7 Participants
|
22.0 scores on a scale
STANDARD_DEVIATION 4.11 • n=5 Participants
|
21.4 scores on a scale
STANDARD_DEVIATION 4.49 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and 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, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.
The Primary Endpoint was the change from baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Total score at Week 8 (End of Study). The ADHD-RS-5 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, 5th Edition (DSM-5) symptoms of ADHD. Each item is rated on a 4-point Likert-type scale from 0 (none) to 3 (severe). 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.
Outcome measures
| Measure |
Placebo
n=97 Participants
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 Participants
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily and compared to placebo
|
400mg SPN-812
n=97 Participants
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily and compared to placebo
|
|---|---|---|---|
|
Efficacy of SPN-812 Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5)
|
-11.7 units on a scale
Standard Error 1.48
|
-17.6 units on a scale
Standard Error 1.43
|
-17.5 units on a scale
Standard Error 1.52
|
SECONDARY outcome
Timeframe: 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, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.
The first Key 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" and 7 = "very much worse." Successful therapy is indicated by a lower overall score in subsequent testing.
Outcome measures
| Measure |
Placebo
n=97 Participants
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 Participants
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily and compared to placebo
|
400mg SPN-812
n=97 Participants
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily and compared to placebo
|
|---|---|---|---|
|
Effect of SPN-812 Assessed by Clinical Global Impression-Improvement (CGI-I) Scale
|
3.1 score on a scale
Standard Error 0.12
|
2.6 score on a scale
Standard Error 0.12
|
2.6 score on a scale
Standard Error 0.12
|
SECONDARY outcome
Timeframe: Baseline and 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, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.
The second Key Secondary Endpoint was the change from baseline in the Conners 3rd Edition - Parent Short Form (C3PS) Composite T-score at Week 8 (End of Study). The Conners 3rd Edition is a focused diagnostic tool for the assessment of ADHD and associated learning, behavior, and emotional problems in children 6 to 18 years of age. The C3PS is completed by a child's parent/guardian and is comprised of 45 items. The parent rates his/her child on the first 43 items of the C3PS using a 4-point Likert scale (0-3; where 0=not at all true \[never, seldom\] and 3=very much true \[very often, very frequently\]) based on past month; the last 2 items are fill-in-the-blank and do not contribute to raw score(s). Raw score is converted to T-score to account for age (6-11 yrs or 12-18 yrs) and sex (male or female); the difference between T-score at Week 8 and the T-score at Baseline is then computed. A lower change from baseline T-score (\<0) at Week 8 represent a better outcome.
Outcome measures
| Measure |
Placebo
n=97 Participants
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 Participants
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily and compared to placebo
|
400mg SPN-812
n=97 Participants
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily and compared to placebo
|
|---|---|---|---|
|
Effect of SPN-812 Assessed by Conners 3 - Parent Short Form (C3PS)
|
-5.3 T-score
Standard Error 1.00
|
-9.1 T-score
Standard Error 0.96
|
-7.8 T-score
Standard Error 1.06
|
SECONDARY outcome
Timeframe: Baseline and 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, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.
The third Key Secondary Endpoint was the change from baseline in the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) Total Average score at Week 8 (End of Study). The WFIRS instrument evaluates ADHD-related functional impairment. The WFIRS-P is completed by the child's parent/guardian and is comprised of 50 items grouped into six domains: Family (10 items), School (10 items, includes learning \[4 items\] and behavior \[6 items\]), Life Skills (10 items), Child's Self-Concept (3 items), Social Activities (7 items), and Risky Activities (10 items). The parent/guardian rates each item on a 4-point Likert scale (0-3; where 0=never or not at all to 3= very often or very much) based on their child's behavior past month. A Total Average score was computed by calculating mean rating of all 50 items (ranging from 0 to 3). Lower change from baseline Total Average scores (\<0) represent a better outcome.
Outcome measures
| Measure |
Placebo
n=97 Participants
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 Participants
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily and compared to placebo
|
400mg SPN-812
n=97 Participants
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily and compared to placebo
|
|---|---|---|---|
|
Effect of SPN-812 Assessed by Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P)
|
-0.24 units on a scale
Standard Error 0.042
|
-0.35 units on a scale
Standard Error 0.041
|
-0.33 units on a scale
Standard Error 0.044
|
SECONDARY outcome
Timeframe: 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, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.
An additional secondary endpoint was the percentage of responders at Week 8 (End of Study). A responder was defined as a subject who had a 50% or greater reduction (improvement) in their change from baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Total score at Week 8 (End of Study). Values range from 0 to 100%. A higher percentage represents a greater number of responders.
Outcome measures
| Measure |
Placebo
n=97 Participants
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 Participants
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily and compared to placebo
|
400mg SPN-812
n=97 Participants
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily and compared to placebo
|
|---|---|---|---|
|
Effect of SPN-812 Assessed by 50% Responder Rate Per the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5)
|
25.8 percentage of subjects
|
36.0 percentage of subjects
|
41.2 percentage of subjects
|
SECONDARY outcome
Timeframe: Baseline and 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, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.
An additional secondary endpoint was the change from baseline in Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF) Total score at Week 8 (End of Study). The PSI-4 questionnaire evaluates the magnitude of stress in the parent-child relationship based on the parent's perception of the child's characteristics, the personal characteristics of the parent, and the interaction between the parent and the child. The PSI-4-SF was developed for parents of children ages 1 month to 12 years. The PSI-4-SF consists of 36 items divided into three domains: parental distress, parent-child dysfunctional interaction, and difficult child. Each item is rated on a 5-point Likert scale, where SD=Strongly Disagree, D=Disagree, NS=Not Sure, A=Agree, and SA=Strongly Agree. The total score ranges between 90 and 450. Lower change from baseline total scores (\<0) represent a better outcome.
Outcome measures
| Measure |
Placebo
n=97 Participants
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 Participants
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily and compared to placebo
|
400mg SPN-812
n=97 Participants
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily and compared to placebo
|
|---|---|---|---|
|
Effect of SPN-812 Assessed by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF)
|
-5.8 units on a scale
Standard Error 1.95
|
-9.2 units on a scale
Standard Error 1.88
|
-11.6 units on a scale
Standard Error 2.01
|
SECONDARY outcome
Timeframe: Baseline and 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, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.
An additional secondary endpoint was the change from baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Hyperactivity/Impulsivity subscale score and Inattention subscale score at Week 8 (End of Study). The ADHD-RS-5 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 DSM-5 symptoms of ADHD, including 9 items for the Hyperactivity/Impulsivity subscale and 9 items for the Inattention subscale. Each item is rated on a 4-point Likert-type scale from 0 (none) to 3 (severe). Each subscale score is calculated by adding the responses of all respective 9 items (range: 0-27; the higher the subscale score, the more severe the Hyperactivity/Impulsivity or Inattention symptoms). Lower change from baseline subscale scores (\<0) represent a better outcome.
Outcome measures
| Measure |
Placebo
n=97 Participants
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 Participants
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily and compared to placebo
|
400mg SPN-812
n=97 Participants
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily and compared to placebo
|
|---|---|---|---|
|
Effect of SPN-812 Assessed by the Hyperactivity/Impulsivity Subscale and the Inattention Subscale of the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5)
Hyperactivity/impulsivity subscale
|
-5.1 units on a scale
Standard Error 0.78
|
-8.4 units on a scale
Standard Error 0.76
|
-8.3 units on a scale
Standard Error 0.81
|
|
Effect of SPN-812 Assessed by the Hyperactivity/Impulsivity Subscale and the Inattention Subscale of the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5)
Inattention subscale
|
-6.2 units on a scale
Standard Error 0.77
|
-8.9 units on a scale
Standard Error 0.74
|
-8.6 units on a scale
Standard Error 0.80
|
SECONDARY outcome
Timeframe: Baseline and 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, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment. There is a lower 'N' for this scale because the scale was only completed by subjects 8 to 11 years of age, since this specific scale is only validated in children 8-18 years of age.
An additional secondary endpoint was the change from baseline in the Conners 3rd Edition - Self Report Short Form (C3-SRS) Composite T score at Week 8 (End of Study). The Conners 3rd Edition is a focused diagnostic tool for assessment of ADHD and associated learning, behavior, and emotional problems in children 6 to 18 years of age. The C3-SRS, validated in 8-18 years olds, is comprised of 41 items. The subject rates himself/herself on the first 39 items of C3-SRS using a 4-point Likert scale (0-3; where 0=not at all true \[never, seldom\] and 3=very much true \[very often, very frequently\] based on past month; the last 2 items are fill-in-the-blank and do not contribute to the raw score(s). Raw score is converted to T-score to account for age (8-11 yrs or 12-18 yrs) and sex (male or female); the difference between T-score at Week 8 and the T-score at Baseline is then computed. A lower change from baseline T-score (\<0) at Week 8 represent a better outcome.
Outcome measures
| Measure |
Placebo
n=59 Participants
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=69 Participants
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily and compared to placebo
|
400mg SPN-812
n=64 Participants
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily and compared to placebo
|
|---|---|---|---|
|
Effect of SPN-812 Assessed by Conners 3 - Self Report Short Form (C3-SRS)
|
-3.3 T-score
Standard Error 1.03
|
-3.9 T-score
Standard Error 0.99
|
-5.4 T-score
Standard Error 1.03
|
SECONDARY outcome
Timeframe: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8Population: 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, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.
An additional secondary endpoint was the percentage of subjects who were "improved" by visit; "improved" was defined as a subject who had a Clinical Global Impression - Improvement (CGI-I) score of 1 = "Very Much Improved" or 2 = "Much Improved". Values range from 0 to 100%. A higher percentage represents a greater number of subjects who were "improved".
Outcome measures
| Measure |
Placebo
n=97 Participants
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 Participants
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily and compared to placebo
|
400mg SPN-812
n=97 Participants
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily and compared to placebo
|
|---|---|---|---|
|
Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"]
Week 1
|
4.1 percentage of subjects
|
13.2 percentage of subjects
|
10.4 percentage of subjects
|
|
Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"]
Week 2
|
14.5 percentage of subjects
|
25.8 percentage of subjects
|
24.9 percentage of subjects
|
|
Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"]
Week 3
|
21.4 percentage of subjects
|
31.3 percentage of subjects
|
36.7 percentage of subjects
|
|
Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"]
Week 4
|
26.6 percentage of subjects
|
41.9 percentage of subjects
|
37.4 percentage of subjects
|
|
Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"]
Week 5
|
32.7 percentage of subjects
|
48.5 percentage of subjects
|
44.4 percentage of subjects
|
|
Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"]
Week 6
|
30.3 percentage of subjects
|
51.0 percentage of subjects
|
49.5 percentage of subjects
|
|
Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"]
Week 7
|
36.1 percentage of subjects
|
51.0 percentage of subjects
|
44.8 percentage of subjects
|
|
Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"]
Week 8
|
35.5 percentage of subjects
|
47.3 percentage of subjects
|
47.8 percentage of subjects
|
Adverse Events
Placebo
200mg SPN-812
400mg SPN-812
Serious adverse events
| Measure |
Placebo
n=103 participants at risk
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 participants at risk
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily
|
400mg SPN-812
n=100 participants at risk
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily
|
|---|---|---|---|
|
Nervous system disorders
Syncope
|
0.00%
0/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
0.00%
0/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
1.0%
1/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
Psychiatric disorders
Suicidal behavior
|
0.00%
0/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
0.00%
0/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
1.0%
1/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
0.93%
1/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
0.00%
0/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
Other adverse events
| Measure |
Placebo
n=103 participants at risk
Placebo oral capsule
Treatment A: Placebo was administered once daily
|
200mg SPN-812
n=107 participants at risk
200mg SPN-812 oral capsule
Treatment B: 200mg SPN-812 was administered once daily
|
400mg SPN-812
n=100 participants at risk
400mg SPN-812 oral capsule
Treatment C: 400mg SPN-812 was administered once daily
|
|---|---|---|---|
|
Nervous system disorders
Somnolence
|
1.9%
2/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
15.0%
16/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
14.0%
14/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
9.3%
10/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
9.0%
9/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
General disorders
Fatigue
|
4.9%
5/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
9.3%
10/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
9.0%
9/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
Nervous system disorders
Headache
|
4.9%
5/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
12.1%
13/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
6.0%
6/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.9%
3/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
5.6%
6/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
6.0%
6/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
Infections and infestations
Nasopharyngitis
|
7.8%
8/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
4.7%
5/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
6.0%
6/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
Psychiatric disorders
Insomnia
|
0.97%
1/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
6.5%
7/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
3.0%
3/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
Psychiatric disorders
Irritability
|
2.9%
3/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
2.8%
3/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
6.0%
6/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
Gastrointestinal disorders
Vomiting
|
0.97%
1/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
0.93%
1/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
7.0%
7/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/103 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
5.6%
6/107 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
0.00%
0/100 • 8 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg/day SPN-812 arm (assigned treatment arm), but received Placebo during the trial (actual treatment arm). Therefore, the number of participants in either arm will differ by 1 between the Participant Flow table and Adverse Events table.
|
Additional Information
Joseph Hull, PhD, Associate Director Clinical Research
Supernus
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER