Dose-optimization in Adolescents Aged 13-17 Diagnosed With Attention-deficit/Hyperactivity Disorder (ADHD) Using Extended-release Guanfacine HCl

NCT ID: NCT01081132

Last Updated: 2021-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 314 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-19
• Study Completion Date: 2013-05-16

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

Conditions

Attention-Deficit/Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Extended-release Guanfacine HCl

Group Type: EXPERIMENTAL

Extended-release Guanfacine Hydrochloride

Intervention Type: DRUG

The test product will be provided as 1, 2, 3, and 4mg tablets. Subjects will be administered a once-daily dose between 1-7mg/day depending on weight.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matching placebo will be provided as 1,2,3, and 4mg tablets. Subjects will be administered a once-daily dose of placebo between 1-7mg/day depending on weight.

Interventions

Extended-release Guanfacine Hydrochloride

The test product will be provided as 1, 2, 3, and 4mg tablets. Subjects will be administered a once-daily dose between 1-7mg/day depending on weight.

Intervention Type: DRUG

Placebo

Matching placebo will be provided as 1,2,3, and 4mg tablets. Subjects will be administered a once-daily dose of placebo between 1-7mg/day depending on weight.

Intervention Type: OTHER

Other Intervention Names

Intuniv

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).

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Harmonex Neuroscience Research

Dothan, Alabama, United States

Clinical Study Centers, LLC

Little Rock, Arkansas, United States

Peninsula Research Associates

Rolling Hills Estates, California, United States

Psychiatric Centers at San Diego (PCSD-Feighner Research Institute)

San Diego, California, United States

Encompass Clinical Research

Spring Valley, California, United States

Elite Clinical Trials, Inc.

Wildomar, California, United States

IMMUNO International Research Centers

Centennial, Colorado, United States

Coastal Connecticut Research LLC

New London, Connecticut, United States

Florida Clinical Research Center, LLC

Bradenton, Florida, United States

Sarkis Clinical Trials

Gainesville, Florida, United States

Amedica Research Institute, Inc.

Hialeah, Florida, United States

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, United States

George M. Joseph, MD, PA

Jacksonville Beach, Florida, United States

Morteza Nadjafi, MD, FAPA

Orlando, Florida, United States

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, United States

Miami Research Associates

South Miami, Florida, United States

Janus Center for Psychiatric Research

West Palm Beach, Florida, United States

Northwest Behavioral Research Center

Roswell, Georgia, United States

Institute for Behavioral Medicine

Smyrna, Georgia, United States

Capstone Clinical Research

Libertyville, Illinois, United States

AMR-Baber Research Inc.

Naperville, Illinois, United States

Goldpoint Clinical Research, LLC

Indianapolis, Indiana, United States

Clinco, Inc.

Terre Haute, Indiana, United States

Psychiatric Associates

Overland Park, Kansas, United States

Four Rivers Clinical Research, Inc.

Paducah, Kentucky, United States

Rochester Center for Behavioral Medicine

Rochester Hills, Michigan, United States

Clinical Neurophysiology Services, PC

Sterling Heights, Michigan, United States

Comprehensive Psychiatric Associates

Gladstone, Missouri, United States

St Charles Psychiatric Associates - Midwest Research Group

Saint Charles, Missouri, United States

Center for Psychiatry and Behavioral Medicine, Inc.

Las Vegas, Nevada, United States

Albuquerque Neuroscience Inc.

Albuquerque, New Mexico, United States

Finger Lakes Clinical Research

Rochester, New York, United States

Richmond Behavioral Associates

Staten Island, New York, United States

Triangle Neuropsychiatry

Durham, North Carolina, United States

NorthCoast Clinical Trials

Beachwood, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

IPS Research Company

Oklahoma City, Oklahoma, United States

Tulsa Clinical Research, LLC

Tulsa, Oklahoma, United States

OCCI, Inc.

Portland, Oregon, United States

Oregon Center for Clinical Investigations, Inc.

Salem, Oregon, United States

CRI Worldwide

Philadelphia, Pennsylvania, United States

University Services Sleep Diagnostic and Treatment Centers

West Chester, Pennsylvania, United States

Rainbow Research

Barnwell, South Carolina, United States

The Jackson Clinic

Jackson, Tennessee, United States

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, United States

Research Strategies of Memphis, LLC

Memphis, Tennessee, United States

FutureSearch Trials

Austin, Texas, United States

InSite Clinical Research

DeSoto, Texas, United States

R/D Clinical Research, Inc.

Lake Jackson, Texas, United States

Westex Clinical Investigations

Lubbock, Texas, United States

Neuroscience, Inc.

Herndon, Virginia, United States

Alliance Research Group

Richmond, Virginia, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

East Side Therapeutic Resource

Kirkland, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26506582 (View on PubMed)

Other Identifiers

2011-002221-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SPD503-312

Identifier Type: -

Identifier Source: org_study_id