SPD503 in Subjects Aged 6-17 Years With Generalized Anxiety Disorder (GAD), Separation Anxiety Disorder (SAD), or Social Phobia (SoP)

A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Safety and Tolerability of SPD503 in Subjects Aged 6-17 Years With Generalized Anxiety Disorder (GAD), Separation Anxiety Disorder (SAD), or Social Phobia (SoP).

This study will evaluate the safety and tolerability of SPD503 in subjects aged 6-17 years with GAD, SAD, or SoP based on treatment emergent adverse events (TEAEs), vital signs and ECGs.

Study Overview

• Status: Completed
• Conditions: Phobia, Social; Anxiety, Separation; Generalized Anxiety Disorder (GAD)
• Intervention / Treatment: Drug: SPD503 (extended-release Guanfacine hydrochloride); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Birmingham Research Group, Inc
  • California
    • Carson, California, United States, 90746
      • Dr. Joseph H. Rodd
    • Imperial, California, United States, 92251
      • Sun Valley Research
    • Irvine, California, United States, 92618
      • Irvine Center for Clinical Research
    • San Diego, California, United States, 92123
      • Sharp Mesa Vista Hospital, Clinical Research Department
    • Wildomar, California, United States, 92595
      • Elite Clinical Trials, Inc
  • Florida
    • Bradenton, Florida, United States, 34201
      • Florida Clinical Research Center
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Winter Park, Florida, United States, 32789
      • Kolin Research Group
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
    • Smyrna, Georgia, United States, 30080-6315
      • Institute of Behavioral Medicine, LLC
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • Midwest Research GRoup
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Premier Psychiatric Group, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center For Psychiatry And Behavioral Medicine, Inc
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical Center
    • New York, New York, United States, 10032
      • Columbia University, NY State Psychiatric Institute
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Durham, North Carolina, United States, 27705-4596
      • Duke University Medical Center, Duke Child and Family Study Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience
    • Cleveland, Ohio, United States, 44012
      • University Hospitals of Cleveland Medical Center
    • Mason, Ohio, United States, 45040
      • Professional Psychiatric Services
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Research Strategies of Memphis, LLC
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Clinical Trials, LP
    • Houston, Texas, United States, 77098
      • Houston Clinical Trials LLC
  • Utah
    • Clinton, Utah, United States, 84015
      • Ericksen Research and Development
  • Virginia
    • Herndon, Virginia, United States, 20170
      • Neuroscience, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Outpatient subjects aged 6-17 years inclusive at the time of consent/assent (Screening Visit [Visit 1] only).
2. Subject's parent or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent by the subject indicating that the subject is aware of the investigational nature of the study and the required procedures in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidance E6 (1996) and applicable regulations before completing any study-related procedures (Screening Visit [Visit 1] only).
3. Subject meets Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) criteria for a Primary Diagnosis of 1 or any combination of the following; GAD, SAD or SoP (300.02, 309.21 and 300.23), based on a detailed psychiatric evaluation at screening including completion of the Anxiety Disorders Interview Schedule for DSM-IV Child Version (ADIS-C).
4. Subject has a score of >/= 4 on the Clinician Severity Rating Scale for the Principal Diagnosis on the ADIS-C CSR) at the Screening Visit (Visit 1) and the Baseline Visit (Visit 2).
5. Subject is functioning at an age-appropriate level intellectually, as determined by the Investigator.
6. Subject and parent/LAR understand, are able, willing, and likely to fully comply with the study procedures and restrictions defined in this protocol, in the opinion of the Investigator.
7. Subject is able to swallow intact tablets.
8. Subjects who are females of child-bearing potential (FOCP), defined as >/= 9 years of age or if <9 years of age are post-menarchal, must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test at the Screening Visit (Visit 1) and a negative urine pregnancy test at the Baseline Visit (Visit 2) and Week 12 (Visit 11/ET). Females of child-bearing potential must abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception.

Exclusion Criteria:

1. Subject has a current co-morbid psychiatric diagnosis of a major depressive disorder, bipolar illness, psychosis, a pervasive development disorder other than Asperger's Syndrome, attention deficit hyperactivity disorder, an eating disorder, or substance abuse disorder.
2. Subject has an ADIS-C CSR score for any Axis I disorder that is greater than the ADIS-C CSR score for their Principal Diagnosis of GAD, SAD, or SoP.
3. Subject has any condition or illness which, in the opinion of the Investigator, represents an inappropriate risk to the subject and/or could confound the interpretation of the study.
4. Within 14 days prior to the Baseline Visit subject has received any evidence-based psychosocial intervention intended to reduce anxiety symptoms i.e. Individual Cognitive Behavioral Therapy, Group Cognitive Behavioral Therapy, or Social Effectiveness Training.
5. Subject has started or changed the type or intensity of a non evidence-based psychosocial intervention intended to reduce anxiety symptoms within 6 weeks prior to the Baseline Visit (Visit 2).
6. Subject has a known history or presence of structural cardiac abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction problems (e.g., clinically significant heart block), exercise-related cardiac events including syncope and pre syncope, or clinically significant bradycardia.
7. Subject with orthostatic hypotension or a known history of controlled or uncontrolled hypertension.
8. Subject has a blood pressure measurement above the 95th percentile for age, sex, and height.
9. Subject has a history of a seizure disorder other than a single childhood febrile seizure occurring before the age of 3 years.
10. Subject is currently considered at risk for suicide in the opinion of the Investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the Investigator.
11. Subject is unable to limit caffeine intake to 2 servings per day throughout participation in the study beginning at time of informed consent/assent.
12. Subject has a history of alcohol or other substance abuse or dependence, as defined by DSM-IV within the last 6 months.
13. Clinically important abnormality on drug and alcohol screen at the Screening Visit (Visit 1) or Baseline Visit (Visit 2).
14. History of failure to respond to 2 adequate trials (consisting of an appropriate dose and adequate duration of therapy) of an SSRI or one trial of cognitive behavioral therapy for the treatment of GAD, SAD, or SoP.
15. Subject is well controlled on anxiolytic pharmacologic or non-pharmacologic therapy with acceptable tolerability.
16. Subject is currently using a prohibited medication or other medications, including herbal supplements that have identified anxiolytic or anxiogenic effects, that affect BP or heart rate or that have CNS effects in violation of the protocol-specified washout criteria at the Baseline Visit (Visit 2).
17. Subject is currently using valproic acid or any drug known to inhibit or induce CYP3A4/5 in violation of the protocol-specified washout criteria at the Baseline Visit (Visit 2).
18. Use of another investigational medicinal product or participation in a clinical study within 30 days prior to the Baseline Visit (Visit 2).
19. Subject is significantly overweight based on Center for Disease Control and Prevention body mass index (BMI)-for-age sex specific charts at the Screening Visit (Visit 1). Significantly overweight is defined as a BMI >95th percentile for this study.
20. Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride or any components found in SPD503.
21. Subject is female and is pregnant or currently lactating.
22. Subject failed screening or was previously enrolled in this study.
23. Subject has another member of the same household currently participating in this study.

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; Once-daily oral dosing in the evening for 12 weeks.
ACTIVE_COMPARATOR: SPD503	Drug: SPD503 (extended-release Guanfacine hydrochloride); Once-daily oral dosing of SPD503 in the evening ranging from 1-6 mg for 12 weeks (6 week dose optimization and 6 week dose maintenance).; Other Names: Intuniv

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Systolic Blood Pressure at Up to 12 Weeks		Baseline and up to 12 weeks
Change From Baseline in Diastolic Blood Pressure at Up to 12 Weeks		Baseline and up to 12 weeks
Change From Baseline in Pulse Rate at Up to 12 Weeks		Baseline and up to 12 weeks
Change From Baseline in Height at up to 12 Weeks		Baseline and up to 12 weeks
Change From Baseline in Weight at up to 12 Weeks		Baseline and up to 12 weeks
Change From Baseline in Electrocardiogram (ECG) QRS Interval at up to 12 Weeks	QRS complex is a portion of the ECG tracing that represents depolarization of the ventricular myocardium.	Baseline and up to 12 weeks
Change From Baseline in ECG QTcF Interval at up to 12 Weeks	The QT interval is the time from the start of the Q wave to the end of the T wave. It is a portion of the ECG tracing that represents the time taken for ventricular depolarisation and repolarisation. The QTcF includes a correction factor to help account for changes in heart rate.	Baseline and up to 12 weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Strawn JR, Compton SN, Robertson B, Albano AM, Hamdani M, Rynn MA. Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial. J Child Adolesc Psychopharmacol. 2017 Feb;27(1):29-37. doi: 10.1089/cap.2016.0132. Epub 2017 Feb 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 4, 2012
• Primary Completion (ACTUAL): July 15, 2013
• Study Completion (ACTUAL): July 15, 2013

Study Registration Dates

• First Submitted: November 9, 2011
• First Submitted That Met QC Criteria: November 9, 2011
• First Posted (ESTIMATE): November 11, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 10, 2021
• Last Update Submitted That Met QC Criteria: May 29, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurodevelopmental Disorders; Disease; Anxiety Disorders; Phobia, Social; Phobic Disorders; Anxiety, Separation; 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: SPD503-210