Clinical trial NCT01470469: SPD503 in Subjects Aged 6-17 Years With Generalized Anxiety Disorder (GAD), Separation Anxiety Disorder (SAD), or Social Phobia (SoP)
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Generalized Anxiety Disorder (GAD)
Anxiety, Separation
Phobia, Social
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-11-11
Enrollment: 83
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Systolic Blood Pressure at Up to 12 Weeks
timeFrame: Baseline and up to 12 weeks
measure: Change From Baseline in Diastolic Blood Pressure at Up to 12 Weeks
timeFrame: Baseline and up to 12 weeks
measure: Change From Baseline in Pulse Rate at Up to 12 Weeks
timeFrame: Baseline and up to 12 weeks
measure: Change From Baseline in Height at up to 12 Weeks
timeFrame: Baseline and up to 12 weeks
measure: Change From Baseline in Weight at up to 12 Weeks
timeFrame: Baseline and up to 12 weeks
measure: Change From Baseline in Electrocardiogram (ECG) QRS Interval at up to 12 Weeks
timeFrame: Baseline and up to 12 weeks
measure: Change From Baseline in ECG QTcF Interval at up to 12 Weeks
timeFrame: Baseline and up to 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Research Group, Inc
state: Alabama
city: Carson
country: United States
facility: Dr. Joseph H. Rodd
state: California
city: Imperial
country: United States
facility: Sun Valley Research
state: California
city: Irvine
country: United States
facility: Irvine Center for Clinical Research
state: California
city: San Diego
country: United States
facility: Sharp Mesa Vista Hospital, Clinical Research Department
state: California
city: Wildomar
country: United States
facility: Elite Clinical Trials, Inc
state: California
city: Bradenton
country: United States
facility: Florida Clinical Research Center
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Winter Park
country: United States
facility: Kolin Research Group
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Smyrna
country: United States
facility: Institute of Behavioral Medicine, LLC
state: Georgia
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine
state: Michigan
city: Saint Charles
country: United States
facility: Midwest Research Group
state: Missouri
city: Lincoln
country: United States
facility: Premier Psychiatric Group, LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine, Inc
state: Nevada
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
city: New York
country: United States
facility: Columbia University, NY State Psychiatric Institute
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Durham
country: United States
facility: Duke University Medical Center, Duke Child and Family Study Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland Medical Center
state: Ohio
city: Mason
country: United States
facility: Professional Psychiatric Services
state: Ohio
city: Middleburg Heights
country: United States
facility: North Star Research
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Memphis
country: United States
facility: Research Strategies of Memphis, LLC
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Clinical Trials, LP
state: Texas
city: Houston
country: United States
facility: Houston Clinical Trials LLC
state: Texas
city: Clinton
country: United States
facility: Ericksen Research and Development
state: Utah
city: Herndon
country: United States
facility: NeuroScience, Inc.
state: Virginia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.