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Evaluation of SPN-812 (Viloxazine Extended-release Capsule) High Dose in Children With ADHD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03247543
Recruitment Status : Completed
First Posted : August 11, 2017
Results First Posted : July 8, 2021
Last Update Posted : July 8, 2021
Sponsor:
Information provided by (Responsible Party):
Supernus Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition ADHD
Interventions Drug: Placebo
Drug: 200mg SPN-812
Drug: 400mg SPN-812
Enrollment 313
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

Period Title: Overall Study
Started [1] 102 107 101 [2]
Completed 85 88 78
Not Completed 17 19 23
Reason Not Completed
Adverse Event             3             6             4
Lost to Follow-up             10             7             8
Consent withdrawn by caregiver             2             2             9
Withdrawal by Subject             0             0             1
Failure to Follow study procedures             1             3             1
Lack of Efficacy             1             0             0
Non-compliance with study visits             0             1             0
[1]
The number of subjects reported here is based on the Safety Population (assigned treatment arm); includes subjects who were randomized and took at least one dose of study medication.
[2]
One subject randomized to the 400mg/day SPN-812 arm received Placebo during the trial.
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812 Total
Hide Arm/Group Description

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

Total of all reporting groups
Overall Number of Baseline Participants 97 107 97 301
Hide Baseline Analysis Population Description
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.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 97 participants 107 participants 97 participants 301 participants
8.5  (1.69) 8.5  (1.71) 8.4  (1.66) 8.4  (1.68)
Age, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 97 participants 107 participants 97 participants 301 participants
Age 6 to 9
64
  66.0%
71
  66.4%
68
  70.1%
203
  67.4%
Age 10 to 11
33
  34.0%
36
  33.6%
29
  29.9%
98
  32.6%
[1]
Measure Analysis Population Description: The sum of each categorical age group is equal to the number of participants in the analysis population.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 97 participants 107 participants 97 participants 301 participants
Female
36
  37.1%
33
  30.8%
38
  39.2%
107
  35.5%
Male
61
  62.9%
74
  69.2%
59
  60.8%
194
  64.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 97 participants 107 participants 97 participants 301 participants
Hispanic or Latino
30
  30.9%
27
  25.2%
34
  35.1%
91
  30.2%
Not Hispanic or Latino
67
  69.1%
80
  74.8%
63
  64.9%
210
  69.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 97 participants 107 participants 97 participants 301 participants
American Indian or Alaska Native
2
   2.1%
0
   0.0%
1
   1.0%
3
   1.0%
Asian
1
   1.0%
0
   0.0%
0
   0.0%
1
   0.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
37
  38.1%
49
  45.8%
39
  40.2%
125
  41.5%
White
53
  54.6%
54
  50.5%
52
  53.6%
159
  52.8%
More than one race
4
   4.1%
4
   3.7%
5
   5.2%
13
   4.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 97 participants 107 participants 97 participants 301 participants
97 107 97 301
ADHD-RS-5 Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 97 participants 107 participants 97 participants 301 participants
43.5  (6.79) 43.8  (6.54) 45.0  (6.55) 44.1  (6.63)
[1]
Measure Description: The Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology. It consists of 18 items that correspond to the 18 ADHD symptoms per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Each item is rated on a 4-point Likert-type scale from 0 (none) to 3 (severe). Total score = sum of 18 items (range: 0 to 54). The higher the score, the more severe the ADHD symptoms (a total score >=28 was an inclusion criterion of this study).
ADHD-RS-5 Inattention Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 97 participants 107 participants 97 participants 301 participants
22.5  (3.20) 22.6  (3.42) 23.0  (3.21) 22.7  (3.28)
[1]
Measure Description: The Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology. It consists of 18 items that correspond to 18 ADHD symptoms per DSM-5, including 9 items for the Hyperactivity/Impulsivity (HI) subscale and 9 items for the Inattention (IA) subscale. Each item is rated on a 4-point Likert-type scale from 0 (none) to 3 (severe). The IA Subscale score = sum of all 9 IA items on the ADHD-RS-5 (range: 0 to 27). The higher the score, the more severe the IA symptoms of ADHD.
ADHD-RS-5 Hyperactivity/Impulsivity Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 97 participants 107 participants 97 participants 301 participants
21.0  (4.78) 21.2  (4.54) 22.0  (4.11) 21.4  (4.49)
[1]
Measure Description: The Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology. It consists of 18 items that correspond to 18 ADHD symptoms per DSM-5, including 9 items for the Hyperactivity/Impulsivity (HI) subscale and 9 items for the Inattention (IA) subscale. Each item is rated on a 4-point Likert-type scale from 0 (none) to 3 (severe). The HI Subscale score = the sum of all 9 HI items on the ADHD-RS-5 (range: 0 to 27). The higher the score, the more severe the HI symptoms of ADHD.
1.Primary Outcome
Title Efficacy of SPN-812 Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5)
Hide Description 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.
Time Frame Baseline and Week 8 (End of Study)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description:

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily and compared to placebo

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily and compared to placebo

Overall Number of Participants Analyzed 97 107 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-11.7  (1.48) -17.6  (1.43) -17.5  (1.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0038
Comments [Not Specified]
Method Mixed Models for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -6.0
Confidence Interval (2-Sided) 95%
-10.0 to -1.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0063
Comments [Not Specified]
Method Mixed Models for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -5.8
Confidence Interval (2-Sided) 95%
-9.9 to -1.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.11
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Effect of SPN-812 Assessed by Clinical Global Impression-Improvement (CGI-I) Scale
Hide Description 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.
Time Frame Week 8 (End of Study)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description:

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

Overall Number of Participants Analyzed 97 107 97
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
3.1  (0.12) 2.6  (0.12) 2.6  (0.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with baseline Clinical Global Impression-Severity of Illness (CGI-S) score and treatment as fixed independent variables.
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-0.8 to -0.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0099
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with baseline Clinical Global Impression-Severity of Illness (CGI-S) score and treatment as fixed independent variables.
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.8 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.17
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Effect of SPN-812 Assessed by Conners 3 - Parent Short Form (C3PS)
Hide Description 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.
Time Frame Baseline and Week 8 (End of Study)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description:

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

Overall Number of Participants Analyzed 97 107 97
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-5.3  (1.00) -9.1  (0.96) -7.8  (1.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0064
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-6.5 to -1.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0917
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-5.3 to 0.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.46
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Effect of SPN-812 Assessed by Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P)
Hide Description 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.
Time Frame Baseline and Week 8 (End of Study)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description:

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

Overall Number of Participants Analyzed 97 107 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.24  (0.042) -0.35  (0.041) -0.33  (0.044)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0651
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.22 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.059
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1680
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.20 to 0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.061
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Effect of SPN-812 Assessed by 50% Responder Rate Per the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5)
Hide Description 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.
Time Frame Week 8 (End of Study)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description:

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

Overall Number of Participants Analyzed 97 107 97
Measure Type: Number
Unit of Measure: percentage of subjects
25.8 36.0 41.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1316
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 10.1
Confidence Interval (2-Sided) 95%
-2.9 to 23.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0276
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 15.4
Confidence Interval (2-Sided) 95%
2.0 to 28.9
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Effect of SPN-812 Assessed by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF)
Hide Description 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.
Time Frame Baseline and Week 8 (End of Study)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description:

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

Overall Number of Participants Analyzed 97 107 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-5.8  (1.95) -9.2  (1.88) -11.6  (2.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2128
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -3.4
Confidence Interval (2-Sided) 95%
-8.7 to 1.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.70
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0409
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -5.8
Confidence Interval (2-Sided) 95%
-11.3 to -0.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.83
Estimation Comments [Not Specified]
7.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Baseline and Week 8 (End of Study)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description:

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

Overall Number of Participants Analyzed 97 107 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Hyperactivity/impulsivity subscale -5.1  (0.78) -8.4  (0.76) -8.3  (0.81)
Inattention subscale -6.2  (0.77) -8.9  (0.74) -8.6  (0.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments This analysis pertains to the Hyperactivity/Impulsivity subscale score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -3.3
Confidence Interval (2-Sided) 95%
-5.4 to -1.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments This analysis pertains to the Hyperactivity/Impulsivity subscale score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0039
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-5.3 to -1.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments This analysis pertains to the Inattention subscale score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0087
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-4.8 to -0.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments This analysis pertains to the Inattention subscale score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0248
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-4.6 to -0.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.09
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Effect of SPN-812 Assessed by Conners 3 - Self Report Short Form (C3-SRS)
Hide Description 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.
Time Frame Baseline and Week 8 (End of Study)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description:

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

Overall Number of Participants Analyzed 59 69 64
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-3.3  (1.03) -3.9  (0.99) -5.4  (1.03)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-3.3 to 2.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1602
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-4.9 to 0.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.45
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"]
Hide Description 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".
Time Frame Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description:

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

Overall Number of Participants Analyzed 97 107 97
Measure Type: Number
Unit of Measure: percentage of subjects
Week 1 4.1 13.2 10.4
Week 2 14.5 25.8 24.9
Week 3 21.4 31.3 36.7
Week 4 26.6 41.9 37.4
Week 5 32.7 48.5 44.4
Week 6 30.3 51.0 49.5
Week 7 36.1 51.0 44.8
Week 8 35.5 47.3 47.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments This analysis pertains to Week 1 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0236
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments This analysis pertains to Week 2 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0505
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments This analysis pertains to Week 3 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1225
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments This analysis pertains to Week 4 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0254
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments This analysis pertains to Week 5 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0261
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments This analysis pertains to Week 6 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0037
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments This analysis pertains to Week 7 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0385
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, 200mg SPN-812
Comments This analysis pertains to Week 8 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0956
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments This analysis pertains to Week 1 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0962
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments This analysis pertains to Week 2 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0744
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments This analysis pertains to Week 3 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0218
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments This analysis pertains to Week 4 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1150
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments This analysis pertains to Week 5 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1086
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments This analysis pertains to Week 6 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0082
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments This analysis pertains to Week 7 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2326
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, 400mg SPN-812
Comments This analysis pertains to Week 8 of treatment.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0883
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Time Frame 8 weeks
Adverse Event Reporting Description 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.
 
Arm/Group Title Placebo 200mg SPN-812 400mg SPN-812
Hide Arm/Group Description

Placebo oral capsule

Treatment A: Placebo was administered once daily

200mg SPN-812 oral capsule

Treatment B: 200mg SPN-812 was administered once daily

400mg SPN-812 oral capsule

Treatment C: 400mg SPN-812 was administered once daily

All-Cause Mortality
Placebo 200mg SPN-812 400mg SPN-812
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/103 (0.00%)   0/107 (0.00%)   0/100 (0.00%) 
Hide Serious Adverse Events
Placebo 200mg SPN-812 400mg SPN-812
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/103 (0.00%)   1/107 (0.93%)   2/100 (2.00%) 
Nervous system disorders       
Syncope  1  0/103 (0.00%)  0/107 (0.00%)  1/100 (1.00%) 
Psychiatric disorders       
Suicidal behavior  1  0/103 (0.00%)  0/107 (0.00%)  1/100 (1.00%) 
Suicidal ideation  1  0/103 (0.00%)  1/107 (0.93%)  0/100 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo 200mg SPN-812 400mg SPN-812
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/103 (27.18%)   77/107 (71.96%)   66/100 (66.00%) 
Gastrointestinal disorders       
Abdominal pain upper  1  3/103 (2.91%)  6/107 (5.61%)  6/100 (6.00%) 
Vomiting  1  1/103 (0.97%)  1/107 (0.93%)  7/100 (7.00%) 
General disorders       
Fatigue  1  5/103 (4.85%)  10/107 (9.35%)  9/100 (9.00%) 
Infections and infestations       
Nasopharyngitis  1  8/103 (7.77%)  5/107 (4.67%)  6/100 (6.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  0/103 (0.00%)  10/107 (9.35%)  9/100 (9.00%) 
Nervous system disorders       
Somnolence  1  2/103 (1.94%)  16/107 (14.95%)  14/100 (14.00%) 
Headache  1  5/103 (4.85%)  13/107 (12.15%)  6/100 (6.00%) 
Psychiatric disorders       
Insomnia  1  1/103 (0.97%)  7/107 (6.54%)  3/100 (3.00%) 
Irritability  1  3/103 (2.91%)  3/107 (2.80%)  6/100 (6.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/103 (0.00%)  6/107 (5.61%)  0/100 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Joseph Hull, PhD, Associate Director Clinical Research
Organization: Supernus
Phone: 240-403-5324
EMail: jhull@supernus.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Supernus Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03247543    
Other Study ID Numbers: 812P303
First Submitted: August 9, 2017
First Posted: August 11, 2017
Results First Submitted: May 24, 2021
Results First Posted: July 8, 2021
Last Update Posted: July 8, 2021