Efficacy and Safety of SPD503 in Combination With Psychostimulants

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of SPD503 in subjects with ADHD when co-administered with psychostimulants in children and adolescents aged 6-17 years with a diagnosis of ADHD with a sub-optimal, partial response to stimulants.

Official Title
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A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multi-Center, Dose Optimization Study Evaluating the Efficacy and Safety of SPD503 in Combination With Psychostimulants in Children and Adolescents Aged 6-17 Years With a Diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD)

Conditions
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ADHD

Intervention / Treatment
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* Drug: SPD503-AM
* Drug: SPD503-PM
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects with ADHD currently taking a stable dose of psychostimulant for at least 4 weeks Aged 6-17 years with a sub-optimal Partial response to stimulants Subjects must be < 95th percentile for BMI with weight >= 55lbs and <= 176lbs

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPD503-AM<br>SPD503 (Guanfacine Extended Release) | Drug: SPD503-AM<br>* SPD503 (Guanfacine Extended Release)-AM Optimized 1-4mg<br>* Other names: Intuniv;|
| Experimental: SPD503-PM<br>SPD503 (Guanfacine Extended Release) | Drug: SPD503-PM<br>* SPD503 (Guanfacine Extended Release)-PM Optimized 1-4mg<br>* Other names: Intuniv;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo matched to Guanfacine Hydrochloride Extended Release<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 8 - Last Observation Carried Forward (LOCF) | The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. | Baseline and weekly up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 8 - LOCF | Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. | Baseline and weekly up to 8 weeks | 
| Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) | Baseline and weekly up to 8 weeks | 
| Change From Baseline in Conners' Global Index - Parent (CGI-P) Total Score at Week 8 - LOCF: Morning Assessment (Before School) | The index contains 10 items. Each item on the scale is scored from a range of 0 (reflecting never, seldom) to 3 (reflecting very often, very frequent) with total scores ranging from 0 to 30. | Baseline and weekly up to 8 weeks | 
| Change From Baseline in Conners' Global Index - Parent (CGI-P) Total Score at Week 8 - LOCF: Evening Assessment (Before Bedtime) | The index contains 10 items. Each item on the scale is scored from a range of 0 (reflecting never, seldom) to 3 (reflecting very often, very frequent) with total scores ranging from 0 30. | Baseline and weekly up to 8 weeks | 
| Percentage of Participants With Improvement on Parent Global Assessment (PGA) at Week 8 - LOCF | Parent Global Assessment (PGA) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. | Baseline and week 8 | 
| Change From Baseline in the Oppositional Subscale of the Conners' Parent Rating Scale-Revised Long Form (CPRS-R:L) Score at Week 8 - LOCF | The oppositional subscale of the CPRS-R:L contains 10 items designed to reflect criteria for oppositional defiance disorder (ODD). Each item is scored on a range from 0 (not true at all) to 3 (very much true) with total scores ranging from 0 to 30. Higher scores are reflective of more severe symptoms. | Baseline and weekly up to 8 weeks | 
| Change From Baseline in Before School Functioning Questionnaire (BSFQ) at Week 8 - LOCF | This scale was designed to assess symptoms of ADHD that typically occur in the morning. The BSFQ consists of two components. The first, a 20-item scale with ratings from 0 (none) to 3 (severe) with a range of 0-60 followed by two questions answered with duration of time (in minutes). The second, a 14-item scale with ratings from 0 (no) to 2 (a lot) with a range of 0-28. The results reported here are from the 20-item scale. Lower scores are better. | Baseline and weekly up to 8 weeks | 
| Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Post Sleep Questionnaire (PSQ) overall rating of quality of sleep. There are 5 rating responses ranging from very poor to very good. No numbers are associated with the rating responses. | Baseline and weekly up to 8 weeks |