SPD503 (Guanfacine Hydrochloride) in ADHD Plus Oppositional Symptoms

Study Overview
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Brief Summary
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To assess efficacy and safety of SPD503(guanfacine hydrochloride) in subjects with ADHD and oppositional symptoms.

Official Title
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A Double-Blind, Randomized, Multi-Center, Flexible Dose Study Evaluating the Efficacy and Safety of SPD503 (Guanfacine Hydrochloride) in Children Aged 6-12 With Symptoms of Oppositionality and a Diagnosis of Attention Deficit/Hyperactivity Disorder

Conditions
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ADHD

Intervention / Treatment
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* Drug: SPD503 (Guanfacine hydrochloride)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects with ADHD and oppositional symptoms ADHD-RS>=24 CGI >=4 T-score of Opp subscale CPRS-R:L >=65 Normal ECG and BP >= 55 lbs

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 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 (Guanfacine hydrochloride)<br> | Drug: SPD503 (Guanfacine hydrochloride)<br>* Subjects will start at 1mg tablet each morning and will subsequently be titrated (in 1 mg weekly increments) to optimal dose based upon tolerance and response to investigational product (not to exceed 4 mg/day).<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Oppositional Subscale of the Conners' Parent Rating Scale-Revised Long Form (CPRS-R:L) Score at Up to 8 Weeks | 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 up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at Up to 8 Weeks | 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 up to 8 weeks | 
| Assessment of Clinical Global Impression-Severity of Illness (CGI-S) | 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) | up to 8 weeks | 
| Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) | 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. | up to 8 weeks | 
| Change From Baseline in the 40-Item Conduct Problem Scale of the New York Parent's Rating Scale-School-aged (NYPRS-S) Score at Up to 8 Weeks | Each item on the NYPRS-S is scored from a range of 0 (not at all) to 3 (very much) with total scores ranging from 0 to 120. Higher scores are reflective of increased disease severity. | Baseline and up to 8 weeks | 
| Change From Baseline in the Parent Stress Index-Short Form (PSI/SF) Score at Up to 8 Weeks | The response to each of the 36 items on the PSI/SF is converted to a five-point scale from 1 (strongly agree) to 5 (strongly disagree) with total scores ranging from 36 to 180. A higher score is reflective of less stress for the parents. | Baseline and up to 8 weeks | 
| Number of Participants With Overall Satisfaction on the Medication Satisfaction Survey (MSS) | The Medication Satisfaction Survey (MSS) consists of 11 questions each being answered with one of six responses (strongly agree, agree, somewhat agree, somewhat disagree, disagree, strongly disagree). Overall satisfaction with their child taking the study medication, Question #11, with a response of strongly agree or agree. | up to 8 weeks | 
| Change From Baseline in Electrocardiogram Results (QTcF Interval) at Up to 8 Weeks | QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate (e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Baseline and up to 8 weeks | 
| Change From Baseline in Pulse Rate at Up to 8 Weeks |  | Baseline and up to 8 weeks | 
| Change From Baseline in Systolic Blood Pressure at Up to 8 Weeks |  | Baseline and up to 8 weeks | 
| Change From Baseline in Diastolic Blood Pressure at Up to 8 Weeks |  | Baseline and up to 8 weeks |