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This was a randomized, double-blind, placebo-controlled, multicenter, 5-arm, parallel-group, dose-ranging study to assess the efficacy and safety of SPN-812 (Viloxazine Extended-release Capsule) in children 6-12 years of age with ADHD.
This study is a randomized, double-blind, placebo-controlled, multicenter, 5-arm, parallel-group, dose-ranging study to assess the efficacy, safety, and tolerability of SPN-812 (Viloxazine Extended-release Capsule) as monotherapy in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children (6-12 years of age). Subjects are randomized in a 1:2:2:2:2 ratio to receive placebo or one of four active treatments (100 mg, 200 mg, 300 mg, or 400 mg SPN-812). The primary objective is to assess the efficacy of SPN-812 in reducing ADHD symptoms as measured by the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo, qd, oral capsule |
|
| 100mg SPN-812 | Experimental | 100mg SPN-812, qd, oral capsule |
|
| 200mg SPN-812 | Experimental | 200mg SPN-812, qd, oral capsule |
|
| 300mg SPN-812 | Experimental | 300mg SPN-812, qd, oral capsule |
|
| 400mg SPN-812 | Experimental | 400mg SPN-812, qd, oral capsule |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo was administered once daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| The Efficacy of SPN-812 on the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) | The Primary Endpoint was the change from baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) Total score at Week 8 (End of Study). The ADHD-RS-IV is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology. The scale consists of 18 items that directly correspond to the 18 Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) symptoms of ADHD. Each item is rated on a 4-point Likert-type scale from 0 (never or rarely) to 3 (very often). A Total score is calculated by adding the responses of all 18 items (range: 0-54; the higher the score, the more severe the ADHD symptoms). Lower change from baseline scores (<0) represent a better outcome. | Baseline to Week 8 (End of Study) |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Scale | The first additional secondary endpoint was the Clinical Global Impression-Improvement (CGI-I) Scale score at Week 8 (End of Study). The CGI-I scale is a single item assessment of how much the patient's illness has improved or worsened relative to a baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point Likert scale from 1 to 7, where 1 = "Very much improved", 2 = "Much improved", 3 = "Minimally improved", 4 = "No change", 5 = "Minimally worse", 6 = "Much worse", and 7 = "Very much worse". Successful therapy is indicated by a lower score (<4) in subsequent testing. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joseph T. Hull, PhD | Supernus Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Florida Clinical Research Center, LLC | Maitland | Florida | 32751 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Treatment A: Placebo was administered once daily |
| FG001 | 100mg SPN-812 | Treatment B: 100mg SPN-812 was administered once daily and compared to placebo |
| FG002 | 200mg SPN-812 | Treatment C: 200mg SPN-812 was administered once daily and compared to placebo |
| FG003 | 300mg SPN-812 | Treatment D: 300mg SPN-812 was administered once daily and compared to placebo |
| FG004 | 400mg SPN-812 | Treatment E: 400mg SPN-812 was administered once daily and compared to placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) assessment, and have at least one post-baseline ADHD-RS-IV assessment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Treatment A: Placebo was administered once daily |
| BG001 | 100mg SPN-812 | Treatment B: 100mg SPN-812 was administered once daily and compared to placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Efficacy of SPN-812 on the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) | The Primary Endpoint was the change from baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) Total score at Week 8 (End of Study). The ADHD-RS-IV is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology. The scale consists of 18 items that directly correspond to the 18 Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) symptoms of ADHD. Each item is rated on a 4-point Likert-type scale from 0 (never or rarely) to 3 (very often). A Total score is calculated by adding the responses of all 18 items (range: 0-54; the higher the score, the more severe the ADHD symptoms). Lower change from baseline scores (<0) represent a better outcome. | Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) assessment and have at least one post-baseline ADHD-RS-IV assessment | Posted | Mean | Standard Deviation | units on a scale | Baseline to Week 8 (End of Study) |
8 Weeks
Number of subjects is based on the Safety Population (defined as subjects who were randomized and took at least one dose of study medication)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Treatment A: Placebo was administered once daily | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joseph Hull, PhD, Director Clinical Research | Supernus | 240-403-5324 | jhull@supernus.com |
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| 100mg SPN-812 | Drug | 100mg SPN-812 was administered once daily and compared to placebo |
|
|
| 200mg SPN-812 | Drug | 200mg SPN-812 was administered once daily and compared to placebo |
|
|
| 300mg SPN-812 | Drug | 300mg SPN-812 was administered once daily and compared to placebo |
|
|
| 400mg SPN-812 | Drug | 400mg SPN-812 was administered once daily and compared to placebo |
|
|
| Week 8 (End of Study) |
| Effect of SPN-812 on the Clinical Global Impression - Severity (CGI-S) Scale | The second additional secondary endpoint was the change from baseline in the Clinical Global Impression-Severity (CGI-S) Scale score at Week 8 (End of Study). The CGI-S scale is a single item clinician/investigator rating of the clinician's assessment of the severity of the ADHD symptoms in relation to the clinician's total experience with patients with ADHD. The CGI-S was rated on a 7-point Likert scale, where 1 = Normal, not at all ill, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Extremely Ill. Successful therapy is indicated by a lower CGI-S score in subsequent testing. A lower change from baseline score (<0) represents a better outcome. | Baseline to Week 8 (End of Study) |
| Adverse Event |
|
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Protocol Violation |
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| Physician Decision |
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| Administrative reason |
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| Multiple reasons |
|
| BG002 | 200mg SPN-812 | Treatment C: 200mg SPN-812 was administered once daily and compared to placebo |
| BG003 | 300mg SPN-812 | Treatment D: 300mg SPN-812 was administered once daily and compared to placebo |
| BG004 | 400mg SPN-812 | Treatment E: 400mg SPN-812 was administered once daily and compared to placebo |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ADHD RS-IV Total Score | The Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) 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, 4th Edition (DSM-IV). Each item is rated on a 4-point Likert-type scale from 0 (never or rarely) to 3 (very often). Total score = sum of 18 items (range: 0 to 54). The higher the score, the more severe the ADHD symptoms (a total score >=26 was an inclusion criterion of this study). | Mean | Standard Deviation | scores on a scale |
|
| ADHD RS-IV Inattention Subscale Score | The Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) 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-IV, 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=never or rarely to 3=very often). The IA Subscale score = sum of all 9 IA items on the ADHD-RS-IV (range:0 to 27). The higher the score, the more severe the IA symptoms of ADHD. | Mean | Standard Deviation | scores on a scale |
|
| ADHD RS-IV Hyperactivity/ Impulsivity Subscale Score | The Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) 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-IV, 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=never or rarely to 3=very often). The HI Subscale score = sum of all 9 HI items on the ADHD-RS-IV (range:0 to 27). The higher the score, the more severe the HI symptoms of ADHD. | Mean | Standard Deviation | scores on a scale |
|
| ID | Title | Description |
|---|
| OG000 | Placebo | Treatment A: Placebo was administered once daily |
| OG001 | 100mg SPN-812 | Treatment B: 100mg SPN-812 was administered once daily and compared to placebo |
| OG002 | 200mg SPN-812 | Treatment C: 200mg SPN-812 was administered once daily and compared to placebo |
| OG003 | 300mg SPN-812 | Treatment D: 300mg SPN-812 was administered once daily and compared to placebo |
| OG004 | 400mg SPN-812 | Treatment E: 400mg SPN-812 was administered once daily and compared to placebo |
|
|
|
| Secondary | Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Scale | The first additional secondary endpoint was the Clinical Global Impression-Improvement (CGI-I) Scale score at Week 8 (End of Study). The CGI-I scale is a single item assessment of how much the patient's illness has improved or worsened relative to a baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point Likert scale from 1 to 7, where 1 = "Very much improved", 2 = "Much improved", 3 = "Minimally improved", 4 = "No change", 5 = "Minimally worse", 6 = "Much worse", and 7 = "Very much worse". Successful therapy is indicated by a lower score (<4) in subsequent testing. | Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) assessment and have at least one post-baseline ADHD-RS-IV assessment | Posted | Mean | Standard Deviation | units on a scale | Week 8 (End of Study) |
|
|
|
|
| Secondary | Effect of SPN-812 on the Clinical Global Impression - Severity (CGI-S) Scale | The second additional secondary endpoint was the change from baseline in the Clinical Global Impression-Severity (CGI-S) Scale score at Week 8 (End of Study). The CGI-S scale is a single item clinician/investigator rating of the clinician's assessment of the severity of the ADHD symptoms in relation to the clinician's total experience with patients with ADHD. The CGI-S was rated on a 7-point Likert scale, where 1 = Normal, not at all ill, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Extremely Ill. Successful therapy is indicated by a lower CGI-S score in subsequent testing. A lower change from baseline score (<0) represents a better outcome. | Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) assessment and have at least one post-baseline ADHD-RS-IV assessment | Posted | Mean | Standard Deviation | units on a scale | Baseline to Week 8 (End of Study) |
|
|
|
|
| 24 |
| 0 |
| 24 |
| 3 |
| 24 |
| EG001 | 100mg SPN-812 | Treatment B: 100mg SPN-812 was administered once daily and compared to placebo | 0 | 48 | 0 | 48 | 23 | 48 |
| EG002 | 200mg SPN-812 | Treatment C: 200mg SPN-812 was administered once daily and compared to placebo | 0 | 48 | 0 | 48 | 22 | 48 |
| EG003 | 300mg SPN-812 | Treatment D: 300mg SPN-812 was administered once daily and compared to placebo | 0 | 48 | 0 | 48 | 30 | 48 |
| EG004 | 400mg SPN-812 | Treatment E: 400mg SPN-812 was administered once daily and compared to placebo | 0 | 49 | 0 | 49 | 30 | 49 |
| Diarrhea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 18.1 | Systematic Assessment |
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| Gastroenteritis viral | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 18.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Irritability | Psychiatric disorders | MedDRA 18.1 | Systematic Assessment |
|
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| Mean Difference (Final Values) |
| -0.4 |
| 2-Sided |
| 95 |
| -1.0 |
| 0.1 |
| Superiority |
| ANOVA | 0.0090 | Mean Difference (Final Values) | -0.8 | 2-Sided | 95 | -1.3 | -0.2 | Superiority |
| ANOVA | 0.0546 | Mean Difference (Final Values) | -0.6 | 2-Sided | 95 | -1.1 | 0.0 | Superiority |
| Mean Difference (Final Values) |
| -0.8 |
| 2-Sided |
| 95 |
| -1.4 |
| -0.1 |
| Superiority |
| ANCOVA | 0.0148 | Mean Difference (Final Values) | -0.8 | 2-Sided | 95 | -1.5 | -0.2 | Superiority |
| ANCOVA | 0.0136 | Mean Difference (Final Values) | -0.9 | 2-Sided | 95 | -1.6 | -0.2 | Superiority |