Maintenance of Efficacy of Extended-Release Guanfacine HCl in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD)

NCT ID: NCT01081145

Last Updated: 2021-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 528 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-11
• Study Completion Date: 2013-06-03

Brief Summary

The primary objective of this study is to evaluate the long-term maintenance of efficacy of Extended-Release Guanfacine HCl in children and adolescents (6-17 years) with attention-deficit/hyperactivity disorder (ADHD) who respond to an initial open-label, short term treatment with SPD503.

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 age and 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 age and 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 age and 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 age and weight.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Male or female, aged 6-17 years at the time of consent/assent at Screening/Visit 1.

2. Subject's parent or legally authorised representative (LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) 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) Guideline E6 (1996) and applicable regulations before completing any study-related procedures at Screening/Visit 1.

3. Subject meets DSM-IV-TR criteria for a primary diagnosis of ADHD, combined subtype, hyperactive/impulsive subtype, or inattentive sub-type based on a detailed psychiatric evaluation using the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL).

4. Subject has a minimum ADHD-RS-IV total score of 32 at Enrolment/Visit 2.

5. Subject has a minimum CGI-S score of 4 at Enrolment/Visit 2.

6. Subject is functioning at an age-appropriate level intellectually, as deemed by the Investigator.

7. Subject and parent/LAR understand, are willing, able, and likely to fully comply with the study requirements, procedures, and restrictions defined in this protocol.

8. Subject is able to swallow intact tablets.

9. Subject who is a female of child-bearing potential (FOCP), defined as 9 years of age or <9 years of age and is post-menarchal, must have a negative serum beta Human Chorionic Gonadotropin (hCG) pregnancy test at Screening/Visit 1 and a negative urine pregnancy test at Enrolment/Visit 2 and agree to comply with any applicable contraceptive requirements of the protocol.

10. Subject has a supine and standing BP measurement within the 95th percentile for age, gender, and height.

Exclusion Criteria

1. Subject has a current, controlled (requiring a prohibited medication or behavioural modification program) or uncontrolled, comorbid psychiatric diagnosis, except oppositional defiant disorder (ODD), including 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 or lifetime history of bipolar illness, psychosis, or conduct disorder 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/Visit 1 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 with orthostatic hypotension or a known history of controlled or uncontrolled hypertension.

5. Subject has clinically significant ECG findings as judged by the Investigator with consideration of the central ECG laboratory's interpretation.

6. Current use of any prohibited medication or other medications, including herbal supplements, that affect BP or heart rate or that have 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]) in violation of the protocol specified washout criteria at Enrolment/Visit 2.

7. Subject has used an investigational product within 30 days prior to Enrolment/Visit 2.

8. Subject is significantly overweight based on Centre for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts. Significantly overweight is defined as a BMI >95th percentile.

9. Children aged 6-12 years with a body weight of <25kg or adolescents aged 13-17 years with a body weight of <34kg or >91kg at Screening/Visit 1.

10. Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride or any components found in SPD503.

11. Clinically important abnormality on drug and alcohol screen (excluding the subject's current ADHD stimulant if applicable) at Screening/Visit 1.

12. Subject has a history of alcohol or other substance abuse or dependence, as defined by DSM-IV-TR (with the exception of nicotine) within the last 6 months.

13. Subject is female and is pregnant or currently lactating.

14. Subject failed screening or was previously enrolled in this study.

15. Subject is currently considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or has a prior history of, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the Investigator (see protocol Section 7.2.4.2 for additional guidance).

16. History of failure to respond to an adequate trial of an alpha 2-agonist for the treatment of ADHD (consisting of an appropriate dose and adequate duration of therapy in the opinion of the Investigator).

17. Subject has a history of a seizure disorder (other than a single childhood febrile seizure occurring before the age of 3 years) or the presence of a serious tic disorder (including Tourette's syndrome).

18. Subject has another member of the same household currently participating in this study.

• Minimum Eligible Age: 6 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

Psychiatric Centers at San Diego, Feighner Research

San Diego, California, United States

Encompass Clinical Research - North Coast

Spring Valley, California, United States

Elite Clinical Trials, Inc.

Wildomar, California, 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

Florida Clinical Research Center, LLC

Maitland, Florida, United States

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, United States

AMR-Baber Research Inc.

Naperville, Illinois, United States

Goldpoint Clinical Research, LLC

Indianapolis, Indiana, United States

Louisiana Research Associates, Inc.

New Orleans, Louisiana, United States

Delmarva Family Resources

Salisbury, Maryland, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Center for Psychiatry and Behavioral Medicine, Inc.

Las Vegas, Nevada, United States

Mount Sinai School of Medicine

New York, New York, United States

Triangle Neuropsychiatry, PLLC

Durham, North Carolina, United States

Ohio State University, Nisonger Center

Columbus, Ohio, United States

IPS Research Company

Oklahoma City, Oklahoma, United States

Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)

Salem, Oregon, United States

CRI Worldwide, LLC

Philadelphia, Pennsylvania, United States

FutureSearch Clinical Trials

Austin, Texas, United States

ADHD Clinic of San Antonio

San Antonio, Texas, United States

Alliance Research Group, LLC

Richmond, Virginia, United States

Eastside Therapeutic Resource

Kirkland, Washington, United States

Ziekenhuis Netwerk Antwerpen

Hoboken, Antwerpen, Belgium

Universitair Ziekenhuis Brussel

Jette, Brussels Capital, Belgium

Universitair Ziekenhuis Gent

Ghent, Oost-vlaanderen, Belgium

Cliniques Universitaires Saint Luc

Brussels, , Belgium

Huisartspraktijk Jaak Mortelmans

Ham, , Belgium

Centre de référence Neuropédiatrique Multidisciplinaire

Namur, , Belgium

Psypluriel

Uccle, , Belgium

Ziekenhuis Inkendaal Koninklijke Instelling v.z.w.

Vlezenbeek, , Belgium

Children's and Women's Health Centre of British Columbia

Vancouver, British Columbia, Canada

JPM van Stralen Medicine Professional Corporation

Ottawa, Ontario, Canada

ADHD Clinic/The Kid's Clinic

Whitby, Ontario, Canada

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Centre Hospitalier de Rouffach

Rouffach, Alsace, France

Hôpital Gui de Chauliac

Montpellier, Languedoc-roussillon, France

Centre Hospitalier Universitaire d'Amiens, Hôpital Nord

Amiens, Picardie, France

Hopitaux Pediatriques de Nice - CHI Lenval

Nice, Provcence Alpes Cote D'Azur, France

Centre Hospitalier Universitaire Bocage-Hôpital d'enfants

Dijon, , France

Hopital Robert Debre Centre pediatrique des pathologies du sommeil

Paris, , France

Hopital Robert-Debre'

Paris, , France

Hopital Gatien de Clocheville CHU de Tours

Tours, , France

Center for Pediatric Clinical Studies

Tübingen, Baden-Wurttemberg, Germany

Universitätsklinik Ulm

Ulm, Baden-Wurttemberg, Germany

Praxis Dr. med. Dipl. Psych. Anton Lindermüller

München, Bavaria, Germany

Medizinisches Studienzentrum Wurzburg

Würzburg, Bavaria, Germany

Sozialpsychiatrisches Centrum Dr. med. Ralph Meyers

Dorsten, North Rhine-Westphalia, Germany

Klinikum der Johannes-Gutenberg-Universität Mainz

Mainz, Rhineland-Palatinate, Germany

Friedrich-Schiller-Universitat Jena

Jena, Thuringia, Germany

Emovis GmbH

Berlin, , Germany

Universitatsklinikum Freiburg

Freiburg im Breisgau, , Germany

Azienda Ospedaliera "Guido Salvini"

Rho, Milan, Italy

IRCCS Fondazione Stella Maris

Calambrone, Pisa, Italy

Azienda Ospedaliero-Universitaria Policlinico-Vittorio

Catania, , Italy

Azienda Osp. Fatebenefratelli - Polo Territoriale UONPIA

Milan, , Italy

Azienda ULSS 16 Padova

Padua, , Italy

Drottning Silvias Barnsjukhus

Roma, , Italy

Università Cattolica del Sacro Cuore

Roma, , Italy

FlevoResearch

Almere Stad, Flevoland, Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, Limburg, Netherlands

Mondriaan Zorggroep Heerlen, Kinder en Jeugdp sychiatrie

Maastricht, , Netherlands

Hospital Son Llàtzer, Laboratorio de Neurociencias IUNICS

Palma, Balearic Islands, Spain

Policlínica Guipuzkoa

Donostia / San Sebastian, Guipuzcoa, Spain

Hospital Fundacion Alcorcon

Alcorcón, Madrid, Spain

Clínica Universitaria de Navarra

Pamplona, Navarre, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Infanta Leonor

Madrid, , Spain

Instituto Valenciano de Neurología Pediatrica

Valencia, , Spain

Barn och Ungdomsmedicin klinik Mölnlycke

Mölnlycke, , Sweden

Norfolk Community Health and Care NHS Trust

Norwich, England, United Kingdom

Ryegate Children's Centre

Sheffield, England, United Kingdom

Centenary House Child and Adolescent Mental Health Services

Sheffield, England, United Kingdom

Queen Elizabeth II Hospital

Welwyn Garden City, England, United Kingdom

Thurrock Community Hospital

Grays, , United Kingdom

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Lister Hospital

Stevenage, , United Kingdom

Countries

United States; Belgium; Canada; France; Germany; Italy; Netherlands; Spain; Sweden; United Kingdom

References

Newcorn JH, Harpin V, Huss M, Lyne A, Sikirica V, Johnson M, Ramos-Quiroga JA, van Stralen J, Dutray B, Sreckovic S, Bloomfield R, Robertson B. Extended-release guanfacine hydrochloride in 6-17-year olds with ADHD: a randomised-withdrawal maintenance of efficacy study. J Child Psychol Psychiatry. 2016 Jun;57(6):717-28. doi: 10.1111/jcpp.12492. Epub 2016 Feb 12.

Reference Type: DERIVED

PMID: 26871297 (View on PubMed)

Other Identifiers

2009-018161-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SPD503-315

Identifier Type: -

Identifier Source: org_study_id