Clinical trial NCT01081132: Dose-optimization in Adolescents Aged 13-17 Diagnosed With Attention-deficit/Hyperactivity Disorder (ADHD) Using Extended-release Guanfacine HCl
Official title: A Phase 3, Double-blind, Randomized, Multi-center, Placebo Controlled, Dose-optimization Study Evaluating the Safety, Efficacy, and Tolerability of Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Adolescents Aged 13-17 Years Diagnosed With Attention-deficit/Hyperactivity Disorder (ADHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Attention-Deficit/Hyperactivity Disorder
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-03-05
Enrollment: 314
Sex: ALL
Minimum age (years): 13
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess the efficacy of optimized Extended-release Guanfacine Hydrochloride compared with placebo in the treatment of adolescents aged 13-17 years with a diagnosis of ADHD as measured by the ADHD-RS-IV


Eligibility criteria: Inclusion Criteria:

1. Male or female, aged 13-17 years at the time of consent/assent (screening 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 and restrictions 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 at screening.
3. Subject meets Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD, combined subtype, or hyperactive/impulsive subtype, based on a detailed psychiatric evaluation using the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime version (K SADS PL) at screening (re-confirm if baseline visit is \>35 days from screening).
4. Subject has a minimum ADHD-RS-IV total score of 32 at baseline.
5. Subject has a minimum CGI-S score of 4 at baseline.
6. Subject is functioning at an age-appropriate level intellectually, as deemed by the Investigator.
7. Subject and parent/LAR understand, are able, willing and likely to fully comply with the study procedures and restrictions defined in this protocol.
8. Subject is able to swallow intact tablets.
9. All females must have a negative serum beta human Chorionic Gonadotropin (hCG) pregnancy test at screening and a negative urine pregnancy test at baseline. Female subjects must abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception.
10. Subject has a supine and standing blood pressure (BP) measurement within the 95th percentile for age, gender, and height.

Exclusion Criteria:

1. Subject has a current, controlled (requiring a prohibited medication or behavioral modification program) or uncontrolled, comorbid psychiatric diagnosis \[except Oppositional Defiant Disorder (ODD), but including all anxiety disorders (except simple phobias)\], all major depressive disorders (dysthymia allowed unless medication required), and any severe comorbid Axis II disorders or severe Axis I disorders such as post traumatic stress disorder, bipolar illness, psychosis, pervasive developmental disorder, obsessive-compulsive disorder, substance abuse disorder, or other symptomatic manifestations that, in the opinion of the Investigator, contraindicate SPD503 treatment or confound efficacy or safety assessments.
2. Subject has any condition or illness including clinically significant abnormal screening laboratory values which, in the opinion of the Investigator, represents an inappropriate risk to the subject and/or could confound the interpretation of the study.
3. 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.
4. Subject has any abnormal or clinically significant ECG findings as judged by the Investigator with consideration of the central ECG interpretation.
5. Subject with orthostatic hypotension or a known history of controlled or uncontrolled hypertension.
6. Current use of any prohibited medication, including herbal supplements that affect blood pressure, heart rate, have central nervous system (CNS) effects, or affect cognitive performance, such as sedating antihistamines and decongestant sympathomimetics (inhaled bronchodilators are permitted) or a history of chronic use of sedating medications (i.e., antihistamines) at baseline.
7. Subject has a history of alcohol or other substance abuse or dependence, as defined by DSM IV-TR (with the exceptions of nicotine) within the last six months.
8. Subject has taken another investigational product within 30 days prior to baseline.
9. Subject is significantly overweight based on Center for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts at screening. Significantly overweight is defined as a BMI \>95th percentile for this study.
10. Body weight of less than 34.0kg or greater than 91.0kg at screening.
11. Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride or any components found in SPD503.
12. Clinically important abnormality on urine drug and/or alcohol screen (excluding the subject's current ADHD stimulant if applicable).
13. Subject is female and is pregnant or currently lactating.
14. Subject failed screening or was previously enrolled in this study.
15. Subject who is currently considered a suicide risk, has previously made a suicide attempt, or has a prior history of, or is currently demonstrating suicidal ideation.
16. History of failure to respond to an adequate trial (consisting of an appropriate dose and adequate duration of therapy), in the opinion of the Investigator, of an α2-agonist for the treatment of ADHD.
17. Subject has a history of a seizure disorder (other than a single childhood febrile seizure occurring before the age of 3 years) or a history of a tic disorder (including Tourette's syndrome).

Primary outcomes:
measure: Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 13
timeFrame: Baseline through week 13
Secondary outcomes:
measure: Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale at the Last On-Treatment Assessment
timeFrame: Baseline through week 13
measure: Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Learning and School Domain Scores at Week 13
timeFrame: Baseline and week 13
measure: Change From Baseline in the WFIRS-P Family Domain Score at Week 13
timeFrame: Baseline and week 13
measure: Change From Baseline in the WFIRS-P Behavior in School Domain Score at Week 13
timeFrame: Baseline and week 13
measure: Change From Baseline in the WFIRS-P Global Domain Score at Week 13
timeFrame: Baseline and week 13
measure: Change From Baseline in the WFIRS-P Risk Domain Score at Week 13
timeFrame: Baseline and week 13
measure: Change From Baseline in the WFIRS-P Social Domain Score at Week 13
timeFrame: Baseline and week 13
measure: Change From Baseline in the WFIRS-P Child Self-Concept Domain Score at Week 13
timeFrame: Baseline and week 13
measure: Change From Baseline in the WFIRS-P Life Skills Domain Score at Week 13
timeFrame: Baseline and week 13
measure: Change From Baseline in the WFIRS-P Academic Performance Domain Score at Week 13
timeFrame: Baseline and week 13
measure: Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores at the Last On-Treatment Assessment
timeFrame: weeks 1 through 13
measure: Changes From Baseline in Behavior Rating Inventory of Executive Function (BRIEF) Scores at Week 13
timeFrame: Baseline and week 13
measure: Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 13
timeFrame: Baseline through week 13
measure: Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Last On-Treatment Assessment
timeFrame: Baseline and week 13
measure: Structure Side-Effect Questionnaire (SSEQ)
timeFrame: Through week 16
measure: Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Through week 16
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Harmonex Neuroscience Research
state: Alabama
city: Little Rock
country: United States
facility: Clinical Study Centers, LLC
state: Arkansas
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates
state: California
city: San Diego
country: United States
facility: Psychiatric Centers at San Diego (PCSD-Feighner Research Institute)
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Wildomar
country: United States
facility: Elite Clinical Trials, Inc.
state: California
city: Centennial
country: United States
facility: IMMUNO International Research Centers
state: Colorado
city: New London
country: United States
facility: Coastal Connecticut Research LLC
state: Connecticut
city: Bradenton
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Hialeah
country: United States
facility: Amedica Research Institute, Inc.
state: Florida
city: Jacksonville Beach
country: United States
facility: George M. Joseph, MD, PA
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Orlando
country: United States
facility: Morteza Nadjafi, MD, FAPA
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: West Palm Beach
country: United States
facility: Janus Center for Psychiatric Research
state: Florida
city: Roswell
country: United States
facility: Northwest Behavioral Research Center
state: Georgia
city: Smyrna
country: United States
facility: Institute for Behavioral Medicine
state: Georgia
city: Libertyville
country: United States
facility: Capstone Clinical Research
state: Illinois
city: Naperville
country: United States
facility: AMR-Baber Research Inc.
state: Illinois
city: Indianapolis
country: United States
facility: Goldpoint Clinical Research, LLC
state: Indiana
city: Terre Haute
country: United States
facility: Clinco, Inc.
state: Indiana
city: Overland Park
country: United States
facility: Psychiatric Associates
state: Kansas
city: Paducah
country: United States
facility: Four Rivers Clinical Research, Inc.
state: Kentucky
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine
state: Michigan
city: Sterling Heights
country: United States
facility: Clinical Neurophysiology Services, PC
state: Michigan
city: Gladstone
country: United States
facility: Comprehensive Psychiatric Associates
state: Missouri
city: Saint Charles
country: United States
facility: St Charles Psychiatric Associates - Midwest Research Group
state: Missouri
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine, Inc.
state: Nevada
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience Inc.
state: New Mexico
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: Triangle Neuropsychiatry
state: North Carolina
city: Beachwood
country: United States
facility: NorthCoast Clinical Trials
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Clinical Research, LLC
state: Oklahoma
city: Portland
country: United States
facility: OCCI, Inc.
state: Oregon
city: Salem
country: United States
facility: Oregon Center for Clinical Investigations, Inc.
state: Oregon
city: Philadelphia
country: United States
facility: CRI Worldwide
state: Pennsylvania
city: West Chester
country: United States
facility: University Services Sleep Diagnostic and Treatment Centers
state: Pennsylvania
city: Barnwell
country: United States
facility: Rainbow Research
state: South Carolina
city: Jackson
country: United States
facility: The Jackson Clinic
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Tennessee
city: Memphis
country: United States
facility: Research Strategies of Memphis, LLC
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials
state: Texas
city: DeSoto
country: United States
facility: InSite Clinical Research
state: Texas
city: Lake Jackson
country: United States
facility: R/D Clinical Research, Inc.
state: Texas
city: Lubbock
country: United States
facility: Westex Clinical Investigations
state: Texas
city: Herndon
country: United States
facility: Neuroscience, Inc.
state: Virginia
city: Richmond
country: United States
facility: Alliance Research Group
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Kirkland
country: United States
facility: East Side Therapeutic Resource
state: Washington
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Wilens TE, Robertson B, Sikirica V, Harper L, Young JL, Bloomfield R, Lyne A, Rynkowski G, Cutler AJ. A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2015 Nov;54(11):916-25.e2. doi: 10.1016/j.jaac.2015.08.016. Epub 2015 Sep 15.