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The purpose of this study is to demonstrate the efficacy, safety, and tolerability of SPN-810 in the treatment of impulsive aggression in patients with Attention-Deficit/Hyperactivity Disorder (ADHD) in conjunction with standard ADHD treatment. Approximately 297 subjects aged 6 to 12 years with ADHD and comorbid impulsive aggression will be recruited in this study. The frequency of impulsive aggression behaviors will be assessed as a primary outcome. Additionally, the severity and improvement in impulsive aggression and quality of life measures for the subject and caregiver will be assessed using validated scales.
This study is a randomized, placebo-controlled, double-blind, multicenter, parallel group, fixed dose study to demonstrate the efficacy, safety, and tolerability of SPN-810 in the treatment of IA in subjects aged 6 to 12 years with ADHD in conjunction with standard ADHD treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low dose SPN-810 (18 mg) | Experimental | Oral |
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| High dose SPN-810 (36 mg) | Experimental | Oral |
|
| Placebo | Placebo Comparator | Oral |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SPN-810 (18 mg) | Drug | Subjects were randomized to receive SPN-810 9 mg 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy and Safety of SPN-810 on the Frequency of Impulsive Aggression (IA) Measured by the Impulsive Aggression Diary | 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. | Daily measure from Visit 2 (Week -2) to Visit 6 (Week 5) for a total of 7 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression - Severity Scale (CGI-S) | 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Metropolitan Neuro Behavioral Institute | Chandler | Arizona | 85226 | United States | ||
| Woodland International Research Group |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 29, 2019 | Nov 10, 2023 |
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|
| SPN-810 (36 mg) | Drug | Subjects were randomized to receive SPN-810 18 mg 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. |
|
| Placebo | Drug | 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. |
|
| 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. |
| Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Investigator Rated | 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 | Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeks |
| Effect of SPN-810 on Impulsive Aggression Measured by Child Health Questionnaire Parent Form 28-item (CHQ-PF28) | 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). | Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks. |
| Effect of SPN-810 on Impulsive Aggression Measured by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF) | 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). | Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks. |
| Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Caregiver Rated | 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 | Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeks |
| Effect of SPN-810 on Impulsive Aggression Measured by the Swanson, Nolan, Pelham Rating Scale- Revised (SNAP-IV) Rating Scale | 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). | Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks. |
| Effect of SPN-810 on Impulsive Aggression Measured by the Percentage of Responders | 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. | Daily measure from Visit 2 (Week -2) to Visit 6 (Week 5) for a total of 7 weeks |
| Little Rock |
| Arkansas |
| 72211 |
| United States |
| Sun Valley Research Center | Imperial | California | 92251 | United States |
| Alliance for Wellness dba Alliance for Research | Long Beach | California | 90807 | United States |
| ASCLEPES Research Center | Panorama City | California | 91402 | United States |
| MCB Clinical Research Centers, LLC | Colorado Springs | Colorado | 80910 | United States |
| Children's National Medical Center/Children's Research Institute | Washington D.C. | District of Columbia | 20310 | United States |
| Gulfcoast Clinical Research Center | Fort Myers | Florida | 33912 | United States |
| Indago Research & Health Center, Inc. | Hialeah | Florida | 33012 | United States |
| Innovative Clinical Research, Inc | Lauderhill | Florida | 33319 | United States |
| Laszlo J. Mate, M.D., P.A. | North Palm Beach | Florida | 71103 | United States |
| APG Research, LLC | Orlando | Florida | 32803 | United States |
| Miami Research Associates | South Miami | Florida | 33143 | United States |
| University of South Florida- Dept. of Psychiatry and Neurosciences | Tampa | Florida | 33613 | United States |
| Atlanta Center for Medical Research | Atlanta | Georgia | 30331 | United States |
| iResearch Atlanta | Decatur | Georgia | 30030 | United States |
| Advanced Clinical Research | Meridian | Idaho | 83642 | United States |
| AMR Conventions Research | Naperville | Illinois | 60563 | United States |
| Pedia Research | Evansville | Indiana | 47715 | United States |
| Pedia Research | Owensboro | Kentucky | 42301 | United States |
| Louisiana State University Health Sciences Center | Shreveport | Louisiana | 71103 | United States |
| St. Charles Psychiatric Associates Midwest Research Center | Saint Charles | Missouri | 63304 | United States |
| Alivation Research, LLC | Lincoln | Nebraska | 68526 | United States |
| Quality Clinical Research | Omaha | Nebraska | 68114 | United States |
| Hassmann Research Institute | Berlin | New Jersey | 08009 | United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| University of Cincinnati Department of Psychiatry and Behavioral Neuroscience | Cincinnati | Ohio | 45219 | United States |
| BioBehavioral Research of Austin P.C. | Austin | Texas | 78759 | United States |
| InSite Clinical Research | DeSoto | Texas | 75115 | United States |
| Houston Clinical Trials | Houston | Texas | United States |
| Ericksen Research & Development | Clinton | Utah | 84015 | United States |
| Pacific Institute of Medical Sciences | Bothell | Washington | 98011 | United States |
| FG001 |
| 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. |
| FG002 | 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. |
|
| Intent-to-Treat | The number of subjects is based on the Intent-to-Treat Population (ITT) which included all subjects who received at least 1 dose of study drug and have a baseline and at least 1 valid post-randomization assessment of frequency of IA behaviors based on IA diary entry. |
|
| Modified Intent-to Treat | The number of subjects is based on the Modified Intent-to-Treat Population (mITT) which included all subjects who received at least 1 dose of study drug and had a Baseline IA frequency ≥6 per week and at least 1 valid post-randomization assessment of frequency of IA behaviors based on IA diary entry. |
|
| COMPLETED | Safety Population only |
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| NOT COMPLETED |
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|
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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Subjects treated with a Placebo |
| BG001 | Low Dose SPN-810 (18 mg) | Subjects treated with low dose of SPN-810 |
| BG002 | High Dose SPN-810 (36 mg) | Subjects treated with high dose of SPN-810 |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Retrospective-Modified Overt Aggression Scale (R-MOAS) | R-MOAS scale gauges the severity of aggressive behavior: the frequency of the 16 behaviors is rated over the past week in 4 areas (a-d). For each open question in each area, the parent rates the aggressive behaviors on a scale from 0 to 5 or more times. To each area corresponds a weighted category: 1(a), 4(b), 2(c) and 3(d). Therefore, the sum of each area yields a maximum weighted score of 20 (a), 120 (b), 60 (c), and 90 (c). The total score is the sum of the four area scores or 0-290; the higher the score, the more severe the aggressive behavior is. | Mean | Standard Deviation | units on a scale |
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| Vitiello Aggression Scale | The Vitiello Aggression Scale is a 10-item rating scale that uses a cluster analysis to categorize aggression into two subtypes; predatory and affective. The predatory score is calculated by summing up the individual scores from items 2, 5, 7, 9, and 10. The affective score is calculated by summing up the individual scores from items 1, 3, 4, 6, and 8. The total score is the difference of predatory score and affective score. Possible range of total score varies from 5 (completely predatory) to -5 (completely affective). | Mean | Standard Deviation | units on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Efficacy and Safety of SPN-810 on the Frequency of Impulsive Aggression (IA) Measured by the Impulsive Aggression Diary | 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. | 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. | Posted | Median | Full Range | Percent Change of IA behaviors | Daily measure from Visit 2 (Week -2) to Visit 6 (Week 5) for a total of 7 weeks |
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| Secondary | Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression - Severity Scale (CGI-S) | 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). | 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. | Posted | Mean | Standard Deviation | score on a scale | 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. |
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| Secondary | Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Investigator Rated | 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 | 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. | Posted | Mean | Standard Deviation | score on a scale | Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeks |
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| Secondary | Effect of SPN-810 on Impulsive Aggression Measured by Child Health Questionnaire Parent Form 28-item (CHQ-PF28) | 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). | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks. |
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| Secondary | Effect of SPN-810 on Impulsive Aggression Measured by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF) | 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). | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks. |
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| Secondary | Effect of SPN-810 on Impulsive Aggression Measured by Clinical Global Impression-Improvement (CGI-I) Scale Caregiver Rated | 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 | 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. | Posted | Mean | Standard Deviation | score on a scale | Visit 4 (Week 1), Visit 5 (Week 2) and Visit 6 (Week 5), a total of 4 weeks |
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| Secondary | Effect of SPN-810 on Impulsive Aggression Measured by the Swanson, Nolan, Pelham Rating Scale- Revised (SNAP-IV) Rating Scale | 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). | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline Visit 3 (Day 1) and Visit 6 (Week 5). Total duration of the study was 5 weeks. |
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| Secondary | Effect of SPN-810 on Impulsive Aggression Measured by the Percentage of Responders | 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. | 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. | Posted | Number | percentage of subjects | Daily measure from Visit 2 (Week -2) to Visit 6 (Week 5) for a total of 7 weeks |
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | 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. | 0 | 94 | 1 | 94 | 13 | 94 |
| EG001 | Low Dose SPN-810 (18 mg) | 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. | 0 | 56 | 0 | 56 | 10 | 56 |
| EG002 | High Dose SPN-810 (36 mg) | 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. | 0 | 142 | 4 | 142 | 23 | 142 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Post-Traumatic Stress Disorder | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Drug Hypersensitivity | Immune system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dystonia | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Aggression | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Blood prolactin increase | Investigations | MedDRA (18.1) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gianpiera Ceresoli-Borroni Director Clinical Research | Supernus Pharmaceuticals | 3018382521 | gceresoliborroni@supernus.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 21, 2020 | Nov 10, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Black or African American |
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| Native Hawaiian or Pacific Islander |
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| White |
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| Other |
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| OG001 |
| High Dose SPN-810 (36 mg) |
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. |
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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. |
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| OG001 | High Dose SPN-810 (36 mg) | SPN-810 (36 mg): 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. |
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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.
| OG001 | High Dose SPN-810 (36 mg) | SPN-810 (36 mg): 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. |
|
|
|
| High Dose SPN-810 (36 mg) |
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. |
|
|
|
| OG001 | High Dose SPN-810 (36 mg) | 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. |
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