SPD503 (Guanfacine Hydrochloride) in ADHD Plus Oppositional Symptoms

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

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

Study Overview

• Status: Completed
• Conditions: ADHD
• Intervention / Treatment: Drug: Placebo; Drug: SPD503 (Guanfacine hydrochloride)

• Study Type: Interventional
• Enrollment (Actual): 217
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85050
      • Hope Research Institute
  • California
    • El Centro, California, United States, 92243
      • Valley Clinical Research
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates Inc
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Hialeah, Florida, United States, 33013
      • Amedica Research Institute, Inc
    • Maitland, Florida, United States, 32751
      • CORE Research, Inc
    • Miami, Florida, United States, 33143
      • Miami Research Associates
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc
    • Winter Park, Florida, United States, 32792
      • Childrens Developmental Center
  • Illinois
    • Libertyville, Illinois, United States, 60048
      • Capstone Clinical Research
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Pedia Research
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Clementon, New Jersey, United States, 08021
      • CRI Worldwide, LLC
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • Rochester, New York, United States, 14618
      • University of Rochester, School of Medicine and Dentistry
    • Syracuse, New York, United States, 13210
      • SUNY Upsate Medical University
  • North Carolina
    • Charlotte, North Carolina, United States, 28226
      • Piedmont Neuropsychiatry
    • Durham, North Carolina, United States, 27705
      • Duke Child & Family Study Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Discovery and Wellness Center for Children
  • Oklahoma
    • Moore, Oklahoma, United States, 73160
      • BHI Inc
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Center for Clinical Investigations, Inc
    • Salem, Oregon, United States, 97301
      • Oregon Center for Clinical Investigations, Inc
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19149
      • CRI Worldwide, LLC
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates, PA
    • Houston, Texas, United States, 77008
      • Claghorn-Lesem Research Clinic Inc
  • Virginia
    • Herndon, Virginia, United States, 20170
      • Neuroscience, Inc
    • Midlothian, Virginia, United States, 23112
      • Dominion Clinical Research
  • Washington
    • Kirkland, Washington, United States, 98033
      • Eastside Therapeutic Resource

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 12 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo
EXPERIMENTAL: SPD503 (Guanfacine hydrochloride)	Drug: SPD503 (Guanfacine hydrochloride); 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Connor DF, Findling RL, Kollins SH, Sallee F, Lopez FA, Lyne A, Tremblay G. Effects of guanfacine extended release on oppositional symptoms in children aged 6-12 years with attention-deficit hyperactivity disorder and oppositional symptoms: a randomized, double-blind, placebo-controlled trial. CNS Drugs. 2010 Sep;24(9):755-68. doi: 10.2165/11537790-000000000-00000.

Helpful Links

• FDA Recall Information
• FDA-approved Label

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 4, 2006
• Primary Completion (ACTUAL): January 4, 2008
• Study Completion (ACTUAL): January 4, 2008

Study Registration Dates

• First Submitted: August 22, 2006
• First Submitted That Met QC Criteria: August 22, 2006
• First Posted (ESTIMATE): August 23, 2006

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 10, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Guanfacine
• Other Study ID Numbers: SPD503-307