Trial Outcomes & Findings for Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 2) (NCT NCT02618434)
NCT ID: NCT02618434
Last Updated: 2024-03-18
Results Overview
The primary efficacy endpoint was percent change (PCHT) in the frequency (unweighted score) of IA behaviors per 7 days in the treatment (titration and maintenance) period relative to the Baseline period calculated over the number of days with non-missing IA diary data. PCHT was then calculated as 100 x (T - B)/B, where T and B are IA behavior frequencies per 7 days during the treatment period (from Day 2 through Visit 6, inclusive) and baseline period (Day ≤1), respectively. The IA behavior frequency per 7 days is defined as (SUM/DAY) x 7, where SUM is the total of the IA behaviors reported in the subject IA diary, and DAY is the number of days with a non-missing IA score in the subject IA diary during the specified study period.
COMPLETED
PHASE3
297 participants
Daily measure from Visit 2 (Week -2) to Visit 6 (Week 5) for a total of 7 weeks
2024-03-18
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo: Subjects were randomized to receive Placebo twice each day (BID) with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
Low Dose SPN-810 (18 mg)
Oral
SPN-810 (18 mg): Subjects were randomized to receive SPN-810 9 mg twice each day (BID) with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
Oral
SPN-810 (36 mg): Subjects were randomized to receive SPN-810 18 mg twice each day (BID) with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|---|
|
Overall Study
STARTED
|
94
|
56
|
142
|
|
Overall Study
Intent-to-Treat
|
92
|
55
|
140
|
|
Overall Study
Modified Intent-to Treat
|
90
|
53
|
135
|
|
Overall Study
COMPLETED
|
84
|
45
|
113
|
|
Overall Study
NOT COMPLETED
|
10
|
11
|
29
|
Reasons for withdrawal
| Measure |
Placebo
Placebo: Subjects were randomized to receive Placebo twice each day (BID) with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
Low Dose SPN-810 (18 mg)
Oral
SPN-810 (18 mg): Subjects were randomized to receive SPN-810 9 mg twice each day (BID) with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
Oral
SPN-810 (36 mg): Subjects were randomized to receive SPN-810 18 mg twice each day (BID) with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
3
|
|
Overall Study
Withdrawal By Parent/Guardian
|
5
|
6
|
9
|
|
Overall Study
Lost to Follow-up
|
3
|
1
|
3
|
|
Overall Study
Adverse Event
|
1
|
0
|
12
|
|
Overall Study
Physician Decision
|
0
|
1
|
0
|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
|
Overall Study
Other, Multiple categories
|
1
|
1
|
1
|
Baseline Characteristics
Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 2)
Baseline characteristics by cohort
| Measure |
Placebo
n=92 Participants
Subjects treated with a Placebo
|
Low Dose SPN-810 (18 mg)
n=55 Participants
Subjects treated with low dose of SPN-810
|
High Dose SPN-810 (36 mg)
n=140 Participants
Subjects treated with high dose of SPN-810
|
Total
n=287 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
9.3 years
STANDARD_DEVIATION 1.66 • n=5 Participants
|
9.0 years
STANDARD_DEVIATION 1.90 • n=7 Participants
|
9.0 years
STANDARD_DEVIATION 1.87 • n=5 Participants
|
9.1 years
STANDARD_DEVIATION 1.81 • n=4 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
56 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
72 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
114 Participants
n=5 Participants
|
231 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
18 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
51 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
74 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
115 Participants
n=5 Participants
|
234 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
32 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
98 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
56 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
91 Participants
n=5 Participants
|
177 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Retrospective-Modified Overt Aggression Scale (R-MOAS)
|
63.91 units on a scale
STANDARD_DEVIATION 33.430 • n=5 Participants
|
66.38 units on a scale
STANDARD_DEVIATION 27.894 • n=7 Participants
|
67.34 units on a scale
STANDARD_DEVIATION 31.949 • n=5 Participants
|
66.06 units on a scale
STANDARD_DEVIATION 31.637 • n=4 Participants
|
|
Vitiello Aggression Scale
|
-3.32 units on a scale
STANDARD_DEVIATION 1.089 • n=5 Participants
|
-3.20 units on a scale
STANDARD_DEVIATION 1.129 • n=7 Participants
|
-3.48 units on a scale
STANDARD_DEVIATION 1.153 • n=5 Participants
|
-3.37 units on a scale
STANDARD_DEVIATION 1.130 • n=4 Participants
|
PRIMARY outcome
Timeframe: Daily measure from Visit 2 (Week -2) to Visit 6 (Week 5) for a total of 7 weeksPopulation: Intent-to-Treat (ITT) Population: The ITT population includes subjects who received at least one dose of the study drug and have a baseline and at least one valid post-randomization assessment of the frequency of IA behaviors based on an IA diary entry. Based on the results of the 810P301 interim analysis, enrollment in the 18 mg of SPN-810 group was halted and subjects planned to receive the 18 mg dose in Stage 2 were randomly assigned to 36 mg of SPN-810 or placebo in a 2:1 ratio.
The primary efficacy endpoint was percent change (PCHT) in the frequency (unweighted score) of IA behaviors per 7 days in the treatment (titration and maintenance) period relative to the Baseline period calculated over the number of days with non-missing IA diary data. PCHT was then calculated as 100 x (T - B)/B, where T and B are IA behavior frequencies per 7 days during the treatment period (from Day 2 through Visit 6, inclusive) and baseline period (Day ≤1), respectively. The IA behavior frequency per 7 days is defined as (SUM/DAY) x 7, where SUM is the total of the IA behaviors reported in the subject IA diary, and DAY is the number of days with a non-missing IA score in the subject IA diary during the specified study period.
Outcome measures
| Measure |
Placebo
n=90 Participants
Subjects were randomized to receive Placebo twice each day with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
n=135 Participants
Subjects were randomized to receive SPN-810 18 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|
|
Efficacy and Safety of SPN-810 on the Frequency of Impulsive Aggression (IA) Measured by the Impulsive Aggression Diary
|
-54.12 Percent Change of IA behaviors
Interval -100.0 to 63.4
|
-51.64 Percent Change of IA behaviors
Interval -100.0 to 105.3
|
SECONDARY outcome
Timeframe: Baseline/Visit 3 (Day 1), Visit 4 (Week 1), Visit 5 (Week 2), and Visit 6 (Week 5). The total duration of the study was 5 weeks.Population: Intent-to-Treat (ITT) Population: The ITT population included subjects who received at least one dose of the study drug and have a baseline and at least one valid post-randomization assessment of the frequency of IA behaviors based on an IA diary entry. Based on the results of the 810P301 interim analysis, enrollment in the 18 mg of SPN-810 group was halted and subjects planned to receive the 18 mg dose in Stage 2 were randomly assigned to 36 mg of SPN-810 or placebo in a 2:1 ratio.
The Clinical Global Impression - Severity of Illness (CGI-S) is a single item clinician rating of clinician's assessment of the severity of IA behaviors CGI-S was evaluated by the Investigator at each visit on a 7- point scale with 1=Normal, 2=Borderline ill, 3=Mildly ill, 4=Moderately ill, 5=Markedly ill, 6=Severely ill, and 7=Extremely ill. Data represent the change between Baseline (Visit 3/Day 1) and three time points: Visit 4 (Week 1); Visit 5 (Week 2) and Visit 6 (Week 5).
Outcome measures
| Measure |
Placebo
n=92 Participants
Subjects were randomized to receive Placebo twice each day with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
n=140 Participants
Subjects were randomized to receive SPN-810 18 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|
|
Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression - Severity Scale (CGI-S)
Visit 4
|
-0.27 score on a scale
Standard Deviation 0.518
|
-0.45 score on a scale
Standard Deviation 0.776
|
|
Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression - Severity Scale (CGI-S)
Visit 5
|
-0.67 score on a scale
Standard Deviation 0.773
|
-0.96 score on a scale
Standard Deviation 1.068
|
|
Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression - Severity Scale (CGI-S)
Visit 6
|
-0.93 score on a scale
Standard Deviation 0.997
|
-1.06 score on a scale
Standard Deviation 1.089
|
SECONDARY outcome
Timeframe: Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeksPopulation: Intent-to-Treat (ITT) Population: The ITT population includes subjects who received at least one dose of the study drug and have a baseline and at least one valid post-randomization assessment of the frequency of IA behaviors based on an IA diary entry. Based on the results of the 810P301 interim analysis, enrollment in the 18 mg of SPN-810 group was halted and subjects planned to receive the 18 mg dose in Stage 2 were randomly assigned to 36 mg of SPN-810 or placebo in a 2:1 ratio.
The Clinical Global Impression - Improvement Scale (CGI-I) is an assessment of how much the patient's illness has improved or worsened relative to a baseline state at the beginning of treatment. CGI-I was evaluated by the Investigator at each visit on a 7-point scale with 1=very much improved, 2= much improved, 3= minimally improved, 4= no change, 5= minimally worse, 6= much worse, 7= very much worse
Outcome measures
| Measure |
Placebo
n=92 Participants
Subjects were randomized to receive Placebo twice each day with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
n=140 Participants
Subjects were randomized to receive SPN-810 18 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|
|
Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Investigator Rated
Visit 6
|
2.8 score on a scale
Standard Deviation 1.13
|
2.5 score on a scale
Standard Deviation 1.04
|
|
Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Investigator Rated
Visit 4
|
3.4 score on a scale
Standard Deviation 0.72
|
3.3 score on a scale
Standard Deviation 0.90
|
|
Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Investigator Rated
Visit 5
|
3.0 score on a scale
Standard Deviation 0.97
|
2.7 score on a scale
Standard Deviation 0.97
|
SECONDARY outcome
Timeframe: Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks.Population: Intent-to-Treat (ITT) Population: The ITT population includes subjects who received at least one dose of the study drug and have a baseline and at least one valid post-randomization assessment of the frequency of IA behaviors based on an IA diary entry. Based on the results of the 810P301 interim analysis, enrollment in the 18 mg of SPN-810 group was halted and subjects planned to receive the 18 mg dose in Stage 2 were randomly assigned to 36 mg of SPN-810 or placebo in a 2:1 ratio.
The CHQ-PF28 is a short generic measure of health status and health-related quality of life. The 28 items have 4, 5, or 6 response options, divided over 8 multi-item scales (physical functioning, general behavior, mental health, self-esteem, general health perceptions, parental impact: emotional, parental impact: time, and family activities) and 5 single item concepts (role functioning: emotional/behavior, role functioning: physical, bodily pain, family cohesion, and change in health). In addition, the individual scale scores will be aggregated to derive 2 summary component scores: the physical functioning and psychosocial health summary scores. The range on subscales and the overall scale is 0-100 (0 = worst possible health state; 100 = best possible health state). Data represent the change from Baseline (Visit 3) to one time point, Visit 6 (Week 5).
Outcome measures
| Measure |
Placebo
n=92 Participants
Subjects were randomized to receive Placebo twice each day with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
n=140 Participants
Subjects were randomized to receive SPN-810 18 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|
|
Effect of SPN-810 on Impulsive Aggression Measured by Child Health Questionnaire Parent Form 28-item (CHQ-PF28)
Physical Functioning Summary Score At Visit 6
|
7.98 score on a scale
Standard Deviation 11.461
|
10.86 score on a scale
Standard Deviation 12.120
|
|
Effect of SPN-810 on Impulsive Aggression Measured by Child Health Questionnaire Parent Form 28-item (CHQ-PF28)
Psychosocial Health Summary Score At Visit 6
|
0.11 score on a scale
Standard Deviation 6.150
|
-2.29 score on a scale
Standard Deviation 9.282
|
SECONDARY outcome
Timeframe: Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks.Population: Intent-to-Treat (ITT) Population: The ITT population includes subjects who received at least one dose of the study drug and have a baseline and at least one valid post-randomization assessment of the frequency of IA behaviors based on an IA diary entry. Based on the results of the 810P301 interim analysis, enrollment in the 18 mg of SPN-810 group was halted and subjects planned to receive the 18 mg dose in Stage 2 were randomly assigned to 36 mg of SPN-810 or placebo in a 2:1 ratio.
The PSI-4-SF is a 36-item self-report measure of parenting stress. Three subscales Parental Distress (PD), Parent-Child Dysfunctional Interaction (P-CDI), and Difficult Child (DC) consist of 12 items each. Parent chooses one of the 5 responses against each item. The 5 responses are: Strongly Agree (SA), Agree (A), Not Sure (NS), Disagree (D), and Strongly Disagree (SD) to indicate the degree to which they agree with each statement. The PD subscale raw score ranges from 12-60, P-CDI and DC each subscale raw score ranges from 16-56. The total stress raw score is the sum of the three subscales (PD+P-CDI+ DC) with a minimum score of 44 and a maximum score of 172. The total stress score is then converted into the percentile score. Parents with a 91st percentile or higher are experiencing clinically significant levels of stress. Data represents the mean change in percentile score from Baseline (Visit 3) and one time point, Visit 6 (Week 5).
Outcome measures
| Measure |
Placebo
n=92 Participants
Subjects were randomized to receive Placebo twice each day with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
n=140 Participants
Subjects were randomized to receive SPN-810 18 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|
|
Effect of SPN-810 on Impulsive Aggression Measured by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF)
Total Score at Visit 6
|
-5.29 score on a scale
Standard Deviation 12.830
|
-7.38 score on a scale
Standard Deviation 15.757
|
|
Effect of SPN-810 on Impulsive Aggression Measured by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF)
Parental Distress Domain at Visit 6
|
-1.02 score on a scale
Standard Deviation 5.486
|
-1.05 score on a scale
Standard Deviation 6.313
|
|
Effect of SPN-810 on Impulsive Aggression Measured by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF)
Parent-Child Dysfunctional Interaction Domain at Visit 6
|
-2.13 score on a scale
Standard Deviation 5.593
|
-2.42 score on a scale
Standard Deviation 6.663
|
|
Effect of SPN-810 on Impulsive Aggression Measured by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF)
Difficult Child Domain at Visit 6
|
-2.14 score on a scale
Standard Deviation 5.898
|
-3.94 score on a scale
Standard Deviation 6.406
|
SECONDARY outcome
Timeframe: Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeksPopulation: Intent-to-Treat (ITT) Population: The ITT population includes subjects who received at least one dose of the study drug and have a baseline and at least one valid post-randomization assessment of the frequency of IA behaviors based on an IA diary entry. Based on the results of the 810P301 interim analysis, enrollment in the 18 mg of SPN-810 group was halted and subjects planned to receive the 18 mg dose in Stage 2 were randomly assigned to 36 mg of SPN-810 or placebo in a 2:1 ratio.
The CGI scale was developed to provide a brief, stand-alone assessment of the clinician's view of a subjects' global functioning prior to and after administration of a study medication. The scale was also rated by the Caregiver to assess the improvement of IA behaviors. . CGI-I was evaluated by the Caregiver at each visit on a 7-point scale with 1=very much improved, 2= much improved, 3= minimally improved, 4= no change, 5= minimally worse, 6= much worse, 7= very much worse
Outcome measures
| Measure |
Placebo
n=92 Participants
Subjects were randomized to receive Placebo twice each day with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
n=140 Participants
Subjects were randomized to receive SPN-810 18 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|
|
Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Caregiver Rated
Visit 4
|
3.1 score on a scale
Standard Deviation 0.95
|
3.1 score on a scale
Standard Deviation 1.02
|
|
Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Caregiver Rated
Visit 5
|
2.9 score on a scale
Standard Deviation 1.14
|
2.7 score on a scale
Standard Deviation 0.94
|
|
Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Caregiver Rated
Visit 6
|
2.7 score on a scale
Standard Deviation 1.26
|
2.5 score on a scale
Standard Deviation 1.12
|
SECONDARY outcome
Timeframe: Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks.Population: Intent-to-Treat (ITT) Population: The ITT population includes subjects who received at least one dose of the study drug and have a baseline and at least one valid post-randomization assessment of the frequency of IA behaviors based on an IA diary entry. Based on the results of the 810P301 interim analysis, enrollment in the 18 mg of SPN-810 group was halted and subjects planned to receive the 18 mg dose in Stage 2 were randomly assigned to 36 mg of SPN-810 or placebo in a 2:1 ratio.
The Swanson, Nolan, Pelham Rating Scale-Revised (SNAP-IV) includes 18 ADHD and 8 oppositional defiant disorder (ODD) symptoms. The symptoms are scored on a 4-point scale, not at all=0, just a little=1, Quite a bit= 2, very much=3. The ratings from the SNAP-IV scale are grouped into the following 4 subscales: ADHD Inattention (items #1-9), ADHD Hyperactivity/Impulsivity (items#10-18), ODD (items# 19-26), and ADHD-combined (first two scales combined, items #1-18). Each observed subscale score is the average rating of the items scores for the subscale where scores range from 0-3; the higher is the score, worsen is the outcome. Data represent the change of the observed scores between Baseline (Visit 3) and the end of the study, Visit 6 (Week 5).
Outcome measures
| Measure |
Placebo
n=92 Participants
Subjects were randomized to receive Placebo twice each day with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
n=140 Participants
Subjects were randomized to receive SPN-810 18 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|
|
Effect of SPN-810 on Impulsive Aggression Measured by the Swanson, Nolan, Pelham Rating Scale- Revised (SNAP-IV) Rating Scale
Inattention subscale
|
-0.33 score on a scale
Standard Deviation 0.539
|
-0.46 score on a scale
Standard Deviation 0.593
|
|
Effect of SPN-810 on Impulsive Aggression Measured by the Swanson, Nolan, Pelham Rating Scale- Revised (SNAP-IV) Rating Scale
Hyperactivity/Impulsivity subscale
|
-0.33 score on a scale
Standard Deviation 0.590
|
-0.50 score on a scale
Standard Deviation 0.681
|
|
Effect of SPN-810 on Impulsive Aggression Measured by the Swanson, Nolan, Pelham Rating Scale- Revised (SNAP-IV) Rating Scale
Oppositional Defiant Disorder subscale
|
-0.50 score on a scale
Standard Deviation 0.685
|
-0.60 score on a scale
Standard Deviation 0.732
|
|
Effect of SPN-810 on Impulsive Aggression Measured by the Swanson, Nolan, Pelham Rating Scale- Revised (SNAP-IV) Rating Scale
Combined subscale
|
-0.33 score on a scale
Standard Deviation 0.501
|
-0.48 score on a scale
Standard Deviation 0.576
|
SECONDARY outcome
Timeframe: Daily measure from Visit 2 (Week -2) to Visit 6 (Week 5) for a total of 7 weeksPopulation: Intent-to-Treat (ITT) Population: The ITT population includes subjects who received at least one dose of the study drug and have a baseline and at least one valid post-randomization assessment of the frequency of IA behaviors based on an IA diary entry. Based on the results of the 810P301 interim analysis, enrollment in the 18 mg of SPN-810 group was halted and subjects planned to receive the 18 mg dose in Stage 2 were randomly assigned to 36 mg of SPN-810 or placebo in a 2:1 ratio.
A Responder was defined as a subject with at least a 30% or 50% reduction in the frequency of IA behaviors per 7 days in the Treatment (Titration and Maintenance) period relative to the Baseline period per the IA Diary. Data represent the percentage of subjects with 30% and 50% reduction in IA behaviors from Baseline to end of treatment period.
Outcome measures
| Measure |
Placebo
n=92 Participants
Subjects were randomized to receive Placebo twice each day with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
n=140 Participants
Subjects were randomized to receive SPN-810 18 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|
|
Effect of SPN-810 on Impulsive Aggression Measured by the Percentage of Responders
≥ 30% Responder
|
73.9 percentage of subjects
|
75.0 percentage of subjects
|
|
Effect of SPN-810 on Impulsive Aggression Measured by the Percentage of Responders
≥ 50% Responder
|
54.3 percentage of subjects
|
51.4 percentage of subjects
|
Adverse Events
Placebo
Low Dose SPN-810 (18 mg)
High Dose SPN-810 (36 mg)
Serious adverse events
| Measure |
Placebo
n=94 participants at risk
Subjects were randomized to receive Placebo twice each day with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
Low Dose SPN-810 (18 mg)
n=56 participants at risk
Subjects were randomized to receive SPN-810 9 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
n=142 participants at risk
Subjects were randomized to receive SPN-810 18 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|---|
|
Psychiatric disorders
Post-Traumatic Stress Disorder
|
1.1%
1/94 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
0.00%
0/56 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
0.00%
0/142 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
|
Immune system disorders
Drug Hypersensitivity
|
0.00%
0/94 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
0.00%
0/56 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
0.70%
1/142 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/94 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
0.00%
0/56 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
0.70%
1/142 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
|
Nervous system disorders
Dystonia
|
0.00%
0/94 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
0.00%
0/56 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
0.70%
1/142 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
|
Psychiatric disorders
Aggression
|
0.00%
0/94 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
0.00%
0/56 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
0.70%
1/142 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
Other adverse events
| Measure |
Placebo
n=94 participants at risk
Subjects were randomized to receive Placebo twice each day with food, in the morning and in the evening, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
Low Dose SPN-810 (18 mg)
n=56 participants at risk
Subjects were randomized to receive SPN-810 9 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
High Dose SPN-810 (36 mg)
n=142 participants at risk
Subjects were randomized to receive SPN-810 18 mg orally twice each day with food, in addition to the stable dose of the optimized ADHD medication determined from the lead-in period. If initiating treatment before noon, patients should start with the morning dose; if afternoon, the evening dose.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
8.5%
8/94 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
5.4%
3/56 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
9.9%
14/142 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
|
Gastrointestinal disorders
Vomiting
|
3.2%
3/94 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
7.1%
4/56 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
4.2%
6/142 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
|
Investigations
Blood prolactin increase
|
2.1%
2/94 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
5.4%
3/56 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
2.1%
3/142 • Visit 3 (Day 1) to Visit 7 (Week 6)-End of Study, a total of 6 weeks
Adverse events reporting pertains to the Safety Population which include all randomized subjects who received at least 1 dose of study drug and have at least one post-randomization safety measurements.
|
Additional Information
Gianpiera Ceresoli-Borroni Director Clinical Research
Supernus Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place