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

NCT01081145 | Completed Phase 3 Results

• 2 other identifiers: SPD503-3152009-018161-12
• Study Type: interventional
• Target: 528
• Locations: 10 countries
• Sites: 81

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase

  Treatment failure was defined as \>= 50% increase (worsening) in ADHD-RS-IV total score and a \>= 2 point increase (worsening) in CGI-S score compared with the respective scores at the Double-blind Randomized-withdrawal Baseline Visit at 2 consecutive Double-blind Randomized-withdrawal Phase visits. Subjects meeting these criteria were regarded as treatment failures regardless of whether or not they were withdrawn. All subjects who discontinued the study for any reason were regarded as treatment failures for the primary analysis.

  26 weeks

Secondary Outcomes (13)

• Time to Treatment Failure During the Double-Blind Randomized-Withdrawal Phase

  26 weeks

• Change From Double-Blind Randomized-Withdrawal Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - Last Observation Carried Forward (LOCF)

  Baseline and week 26

• Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale During the Double-Blind Randomized-Withdrawal Phase - LOCF

  26 weeks

• Change From Double-Blind Randomized-Withdrawal Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - LOCF

  Baseline and week 26

• Health Utilities Index-2/3 (HUI 2/3) Scores During the Double-Blind Randomized-Withdrawal Phase - LOCF

  26 weeks

Study Arms (2)

Extended-release Guanfacine HCl

EXPERIMENTAL

Drug: Extended-release Guanfacine Hydrochloride

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Extended-release Guanfacine Hydrochloride 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.

Extended-release Guanfacine HCl

Placebo 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.

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female, aged 6-17 years at the time of consent/assent at Screening/Visit 1.
• 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.
• 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).
• Subject has a minimum ADHD-RS-IV total score of 32 at Enrolment/Visit 2.
• Subject has a minimum CGI-S score of 4 at Enrolment/Visit 2.
• Subject is functioning at an age-appropriate level intellectually, as deemed by the Investigator.
• Subject and parent/LAR understand, are willing, able, and likely to fully comply with the study requirements, procedures, and restrictions defined in this protocol.
• Subject is able to swallow intact tablets.
• 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.
• Subject has a supine and standing BP measurement within the 95th percentile for age, gender, and height.

You may not qualify if:

• 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.
• 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.
• 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.
• Subject with orthostatic hypotension or a known history of controlled or uncontrolled hypertension.
• Subject has clinically significant ECG findings as judged by the Investigator with consideration of the central ECG laboratory's interpretation.
• 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.
• Subject has used an investigational product within 30 days prior to Enrolment/Visit 2.
• 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.
• 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.
• Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride or any components found in SPD503.
• Clinically important abnormality on drug and alcohol screen (excluding the subject's current ADHD stimulant if applicable) at Screening/Visit 1.
• 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.
• Subject is female and is pregnant or currently lactating.
• Subject failed screening or was previously enrolled in this study.
• 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).

Sponsors & Collaborators

• Shire: lead

Study Sites (81)

Harmonex Neuroscience Research

Dothan, Alabama, 36303, United States

Location

Clinical Study Centers, LLC

Little Rock, Arkansas, 72205, United States

Location

Psychiatric Centers at San Diego, Feighner Research

San Diego, California, 92108, United States

Location

Encompass Clinical Research - North Coast

Spring Valley, California, 91978, United States

Location

Elite Clinical Trials, Inc.

Wildomar, California, 92595, United States

Location

Florida Clinical Research Center, LLC

Bradenton, Florida, 34208, United States

Location

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

Amedica Research Institute, Inc.

Hialeah, Florida, 33013, United States

Location

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, 32216, United States

Location

Florida Clinical Research Center, LLC

Maitland, Florida, 32751, United States

Location

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, 32806, United States

Location

AMR-Baber Research Inc.

Naperville, Illinois, 60563, United States

Location

Goldpoint Clinical Research, LLC

Indianapolis, Indiana, 46260, United States

Location

Louisiana Research Associates, Inc.

New Orleans, Louisiana, 70114, United States

Location

Delmarva Family Resources

Salisbury, Maryland, 21801, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Center for Psychiatry and Behavioral Medicine, Inc.

Las Vegas, Nevada, 89128, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Triangle Neuropsychiatry, PLLC

Durham, North Carolina, 27707, United States

Location

Ohio State University, Nisonger Center

Columbus, Ohio, 43210, United States

Location

IPS Research Company

Oklahoma City, Oklahoma, 73103, United States

Location

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

Salem, Oregon, 97301, United States

Location

CRI Worldwide, LLC

Philadelphia, Pennsylvania, 19139, United States

Location

FutureSearch Clinical Trials

Austin, Texas, 78756, United States

Location

ADHD Clinic of San Antonio

San Antonio, Texas, 78247, United States

Location

Alliance Research Group, LLC

Richmond, Virginia, 23230, United States

Location

Eastside Therapeutic Resource

Kirkland, Washington, 98033, United States

Location

Ziekenhuis Netwerk Antwerpen

Hoboken, Antwerpen, 2660, Belgium

Location

Universitair Ziekenhuis Brussel

Jette, Brussels Capital, 1090, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Oost-vlaanderen, 9000, Belgium

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Huisartspraktijk Jaak Mortelmans

Ham, 3945, Belgium

Location

Centre de référence Neuropédiatrique Multidisciplinaire

Namur, 5000, Belgium

Location

Psypluriel

Uccle, 1180, Belgium

Location

Ziekenhuis Inkendaal Koninklijke Instelling v.z.w.

Vlezenbeek, 1602, Belgium

Location

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

Vancouver, British Columbia, V6H3N1, Canada

Location

JPM van Stralen Medicine Professional Corporation

Ottawa, Ontario, K2G1W2, Canada

Location

ADHD Clinic/The Kid's Clinic

Whitby, Ontario, L1N8M7, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, S7N-OW8, Canada

Location

Centre Hospitalier de Rouffach

Rouffach, Alsace, 68250, France

Location

Hôpital Gui de Chauliac

Montpellier, Languedoc-roussillon, 34295, France

Location

Centre Hospitalier Universitaire d'Amiens, Hôpital Nord

Amiens, Picardie, 80054, France

Location

Hopitaux Pediatriques de Nice - CHI Lenval

Nice, Provcence Alpes Cote D'Azur, 06200, France

Location

Centre Hospitalier Universitaire Bocage-Hôpital d'enfants

Dijon, 21033, France

Location

Hopital Robert Debre Centre pediatrique des pathologies du sommeil

Paris, 75 015, France

Location

Hopital Robert-Debre'

Paris, 75935, France

Location

Hopital Gatien de Clocheville CHU de Tours

Tours, 37 000, France

Location

Center for Pediatric Clinical Studies

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Universitätsklinik Ulm

Ulm, Baden-Wurttemberg, 89075, Germany

Location

Praxis Dr. med. Dipl. Psych. Anton Lindermüller

München, Bavaria, 81241, Germany

Location

Medizinisches Studienzentrum Wurzburg

Würzburg, Bavaria, 97070, Germany

Location

Sozialpsychiatrisches Centrum Dr. med. Ralph Meyers

Dorsten, North Rhine-Westphalia, 46282, Germany

Location

Klinikum der Johannes-Gutenberg-Universität Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Friedrich-Schiller-Universitat Jena

Jena, Thuringia, 07743, Germany

Location

Emovis GmbH

Berlin, 10629, Germany

Location

Universitatsklinikum Freiburg

Freiburg im Breisgau, 79104, Germany

Location

Azienda Ospedaliera "Guido Salvini"

Rho, Milan, 20017, Italy

Location

IRCCS Fondazione Stella Maris

Calambrone, Pisa, 56018, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico-Vittorio

Catania, 95123, Italy

Location

Azienda Osp. Fatebenefratelli - Polo Territoriale UONPIA

Milan, 20129, Italy

Location

Azienda ULSS 16 Padova

Padua, 35143, Italy

Location

Drottning Silvias Barnsjukhus

Roma, 00168, Italy

Location

Università Cattolica del Sacro Cuore

Roma, 00168, Italy

Location

FlevoResearch

Almere Stad, Flevoland, 1311 RL, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, Limburg, 6229 HX, Netherlands

Location

Mondriaan Zorggroep Heerlen, Kinder en Jeugdp sychiatrie

Maastricht, 6229, Netherlands

Location

Hospital Son Llàtzer, Laboratorio de Neurociencias IUNICS

Palma, Balearic Islands, 07198, Spain

Location

Policlínica Guipuzkoa

Donostia / San Sebastian, Guipuzcoa, 20009, Spain

Location

Hospital Fundacion Alcorcon

Alcorcón, Madrid, 289221, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Infanta Leonor

Madrid, 28031, Spain

Location

Instituto Valenciano de Neurología Pediatrica

Valencia, 46010, Spain

Location

Barn och Ungdomsmedicin klinik Mölnlycke

Mölnlycke, 435 30, Sweden

Location

Norfolk Community Health and Care NHS Trust

Norwich, England, NR4 7PA, United Kingdom

Location

Ryegate Children's Centre

Sheffield, England, S10 5DD, United Kingdom

Location

Centenary House Child and Adolescent Mental Health Services

Sheffield, England, S6 3BR, United Kingdom

Location

Queen Elizabeth II Hospital

Welwyn Garden City, England, AL7 4HQ, United Kingdom

Location

Thurrock Community Hospital

Grays, RM16 2PX, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L12 2AP, United Kingdom

Location

Lister Hospital

Stevenage, SG1 4AB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26871297 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2010
• First Posted: March 5, 2010
• Study Start: May 11, 2010
• Primary Completion: June 3, 2013
• Study Completion: June 3, 2013
• Last Updated: June 14, 2021
• Results First Posted: June 9, 2014

Record last verified: 2021-06

Locations

US (27); CA (4); FR (8); BE (8); NL (3); DE (9); SE (1); ES (7); IT (7); GB (7)