Tolerability and Efficacy of AM and PM Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Children 6-12 With Attention-Deficit/Hyperactivity Disorder (ADHD) (The ADHD Tempo Study)

Study Overview
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Brief Summary
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The primary purpose is to assess the efficacy of once daily dosing with optimized SPD503 (1, 2, 3 and 4mg/day), dosed either in the morning or evening, compared to placebo, in children with ADHD as measured by change from baseline score at endpoint on the ADHD-RS-IV.

Official Title
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A Phase 3, Double-blind, Randomized, Multicenter, Placebo-controlled, Dose Optimization Study Evaluating the Tolerability and Efficacy of AM and PM Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Children Aged 6-12 With a Diagnosis of Attention-Deficit/Hyperactivity Disorder

Conditions
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Attention-Deficit/Hyperactivity Disorder

Intervention / Treatment
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* Drug: extended-release guanfacine hydrochloride (SPD503)
* Drug: placebo
* Drug: extended-release guanfacine hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 6-12 years old ADHD diagnosis ADHD-RS-IV minimum score of 28 CGI-S score > or = 4 Exclusion Criteria: Current, controlled or uncontrolled, comorbid psychiatric diagnosis Condition or illness which represent inappropriate risk to subject Known history or presence of structural cardiac abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction problems, exercise-related cardiac events, or clinically significant bradycardia; orthostatic hypotension or controlled or uncontrolled hypertension Use of prohibited medication that have CNS effects or affect cognitive performance History of alcohol or substance abuse within 6 months Current use of medication that affect BP or heart rate Significantly overweight Weight of less than 55 lbs Known allergy to SPD503 Abnormal urine drug and alcohol screen

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: Extended-release Guanfacine Hydrochloride (SPD503) AM<br> | Drug: extended-release guanfacine hydrochloride (SPD503)<br>* dosed in AM<br>* Other names: Intuniv;|
| Experimental: placebo<br> | Drug: placebo<br>* dosed in the AM or PM<br>|
| Experimental: SPD503 PM<br> | Drug: extended-release guanfacine hydrochloride<br>* Dosed in the PM<br>* Other names: Intuniv;|

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-IV (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 up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 up to 8 weeks | 
| Improvement on Clinical Global Impression-Improvement (CGI-I) Scale 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 includes a score of 1 (very much improved) or 2 (much improved) on the scale. | up to 8 weeks | 
| Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 8 - LOCF | The Pediatric Daytime Sleepiness Scale (PDSS) is an 8 question questionnaire scored on a scale from 0 (never) to 4 (always). Total scores range from 0 to 32, with increasing score reflecting greater sleepiness. | Baseline and up to 8 weeks | 
| Change From Baseline in Health Utilities Index-2/3 (HUI 2/3) Scores at Week 8 - LOCF | HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status. | Baseline and up to 8 weeks | 
| Change From Baseline in Conner's Parent Rating Scale - Revised Short Version (CPRS-R:S) Score at Week 8 - LOCF | The Conner's Parent rating Scale-revised short version (CPRS-R) consists of 27 questions graded on a scale from 0 (not true at all) to 3 (very much true) with a total score ranging from 0 to 81. Higher scores are indicative of increased ADHD. This scale allows parents to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior. | Baseline and up to 8 weeks | 
| Change From Baseline in the Bedtime Resistance Subscale of Child's Sleep Habits Questionnaire (CSHQ) at Week 8 - LOCF | The bedtime resistance subscale of CSHQ consists of 6 items scored on a scale from 1 (never/rarely) to 3 (Usually). A higher score reflects more disturbed sleep behavior. | Baseline and 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. | up to 8 weeks | 
| Change From Baseline in Mean Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 8 - LOCF | The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Mean scores range from 0 to 3. | Baseline and up to 8 weeks | 
| Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF |  | Baseline and up to 8 weeks | 
| Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF |  | Baseline and up to 8 weeks | 
| Change From Baseline in Pulse Rate at Week 8 - LOCF |  | Baseline and up to 8 weeks | 
| Change From Baseline in Oral Temperature at Week 8 - LOCF |  | Baseline and up to 8 weeks | 
| Change From Baseline in Height at Week 8 - LOCF |  | Baseline and up to 8 weeks | 
| Change From Baseline in Weight at Week 8 - LOCF |  | Baseline and up to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD