Efficacy and Safety of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)

NCT01244490 | Completed Phase 3 Results DMC

• 2 other identifiers: SPD503-3162010-018579-12
• Study Type: interventional
• Target: 338
• Locations: 13 countries
• Sites: 66

Brief Summary

For children and adolescents, how does SPD503 compare to placebo for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD).

Conditions

Attention Deficit Hyperactivity Disorder

Keywords

ADHD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 10/13 - Last Observation Carried Forward (LOCF)

  The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

  Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Secondary Outcomes (15)

• Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores

  Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

• Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Learning and School Domain Scores at Week 10/13 - LOCF

  Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

• Change From Baseline in the WFIRS-P Family Domain Score at Week 10/13 - LOCF

  Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

• Clinical Global Impression-Severity of Illness (CGI-S) - LOCF

  Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

• Health Utilities Index-2/3 (HUI 2/3) Scores - LOCF

  Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Study Arms (3)

Extended-release Guanfacine Hydrochloride

EXPERIMENTAL

Drug: Extended-release Guanfacine Hydrochloride

Atomoxetine Hydrochloride

OTHER

Active Reference

Drug: Atomoxetine Hydrochloride

Placebo

PLACEBO COMPARATOR

Drug: Placebo Comparator

Interventions

Extended-release Guanfacine Hydrochloride DRUG

Tablet, once daily, optimised dose (1mg to 7mg based on age and weight), 6-week maintenance duration on optimised dose.

Also known as: Intuniv

Extended-release Guanfacine Hydrochloride

Atomoxetine Hydrochloride DRUG

Capsule, once daily, optimised dose (10mg to 100mg based on weight), 8-9-weeks maintenance duration on optimised dose

Also known as: Strattera

Atomoxetine Hydrochloride

Placebo Comparator DRUG

Placebo

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) Guidance E6, and applicable regulations before completing any study related procedures at Screening (Visit 1).
• Subject meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD, combined sub-type, hyperactive/impulsive sub-type, 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 Baseline (Visit 2).
• Subject has a minimum CGI-S score of 4 at Baseline (Visit 2).
• Subject is functioning at an age-appropriate level intellectually, as judged by the Investigator.
• Subject and parent/LAR understand, are willing, able, and likely to fully comply with the study procedures and restrictions defined in this protocol.
• Subject is able to swallow intact tablets and capsules.
• Subject who is a female of child-bearing potential (FOCP), defined as greater than or equal to 9 years of age or \<9 years of age and is menarchal, must have a negative serum beta Human Chorionic Gonadotropin (hCG) pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at Baseline (Visit 2) and agree to comply with any applicable contraceptive requirements of the protocol.
• Subject has supine and standing blood pressure (BP) measurement within the 95th percentile for age, sex, and height

You may not qualify if:

• Subject has a current, controlled (requiring a prohibited medication or behavioural modification program) or uncontrolled, co-morbid psychiatric diagnosis \[except oppositional defiant disorder (ODD)\], including any severe co-morbid Axis II disorders or severe Axis I disorders such as post traumatic stress disorder (PTSD), bipolar illness, psychosis, pervasive developmental disorder, obsessive-compulsive disorder (OCD), 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 treatment with SPD503 or STRATTERA or confound efficacy or safety assessments.
• Subject is well-controlled on their current medication, with acceptable tolerability, and the parent/caregiver does not object to the current medication.
• Subject has a known history or presence of structural cardiac abnormalities, cardiovascular or cerebrovascular disease, serious heart rhythm abnormalities, syncope, tachycardia, cardiac conduction problems (eg, clinically significant heart block or QT interval prolongation), exercise-related cardiac events including syncope and pre syncope, or clinically significant bradycardia.
• Subject has a known family history of sudden cardiac death, ventricular arrhythmia, or QT prolongation.
• Subjects with orthostatic hypotension or a known history of hypertension.
• Subject has glaucoma.
• Subject has clinically significant ECG findings as judged by the Investigator with consideration of the central ECG laboratory's interpretation.
• 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.
• Current use of any prohibited medication or other medications, including monoamine oxidase inhibitors, herbal supplements, that affect BP or heart rate potent CYP2D6 inhibitors, medications known to prolong the QT/QTc interval, medications that lower seizure threshold, pressor agents, beta-2 agonists, medications that affect noradrenaline, medications that 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 \[ie, antihistamines\]) in violation of the protocol specified washout criteria at Baseline (Visit 2).
• Subject has a history of alcohol or other substance abuse or dependence, as defined by DSM-IV (with the exception of nicotine) within the last 6 months.
• Subject has taken another investigational product within 30 days prior to Baseline (Visit 2).
• Subject is significantly overweight based on Center for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts at the Screening (Visit 1). Significantly overweight is defined as a BMI \>95th percentile.
• Children aged 6 12 years with a body weight of less than 25kg or adolescents aged 13 17 years with a body weight of less than 34kg or greater than 91kg at Screening (Visit 1).
• Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride or atomoxetine hydrochloride, or any components found in SPD503 or STRATTERA.
• Clinically important abnormality on drug and alcohol screen (excluding the subject's current ADHD stimulant if applicable) at Screening (Visit 1)

Sponsors & Collaborators

• Shire: lead

Study Sites (66)

Psychiatric Centers at San Diego, Feighner Research

San Diego, California, 92108, United States

Location

Florida Clinical Research Center, LLC

Maitland, Florida, 32751, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30308, United States

Location

Psychiatric Associates

Overland Park, Kansas, 66211, United States

Location

Rochester Center for Behavioral Medicine

Rochester Hills, Michigan, 48307, United States

Location

University of Nebraska Medical Center, Dept. of Psychiatry

Omaha, Nebraska, 68198-5581, United States

Location

Innovis Health

Fargo, North Dakota, 58103, United States

Location

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, 38119, United States

Location

Claghorn-Lesem Research Clinic

Houston, Texas, 77008, United States

Location

R/D Clincial Research, Inc.

Lake Jackson, Texas, 77566, United States

Location

NeuroScience Inc.

Herndon, Virginia, 20170, United States

Location

Medizinische Universitat Graz-Universitaklinik fur Kinder-und Jugendheilkunde

Graz, 8036, Austria

Location

Institut für Psychosomatik

Vienna, 1010, Austria

Location

Dr Grazyna B. Jackiewicz, MD

Niagara Falls, Ontario, L2E 6A4, Canada

Location

JPM Van Stralen Medicine Professional Corp.

Ottawa, Ontario, K2G 1W2, Canada

Location

Centre HospitalierUniversitaire d'Amiens, Hoptial Nord

Amiens, Picardie, 80054, France

Location

Centre Hospitalier Charles Perens - Service de Psychiatrie de l'Enfant et de l'Adolescent

Bordeaux, 33076, France

Location

Centre Hospitalier des Pyrenees

Chartres, 28018, France

Location

Praxis Dr. Wolff

Hagen, North Rhine-Westphalia, 58093, Germany

Location

Praxis Dr. Andreas Mahler

Achim, 28832, Germany

Location

Emovis GmbH

Berlin, 10629, Germany

Location

Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden

Dresden, 01307, Germany

Location

Praxisgemeinschaft Drs. Willem Geraets/Gabriele Lucassen

Düsseldorf, 40215, Germany

Location

Praxis Dr. Walter Robert Otto

Fulda, 36037, Germany

Location

Praxis Dr. Friedrich Kaiser un Ingrid Marinesse

Hamburg, 22415, Germany

Location

Institut fur Ganzheitiche Medzin und Wissenschaft GmbH

Hüttenberg, 35625, Germany

Location

Klinikum der Johannes-Guttenberg-Universitat Mainz

Mainz, 55131, Germany

Location

Zentralinstitut fur Seelische Geseundheit Mannheim Klinik for Psuchiatrie und Psychotherapie des Kindes

Mannheim, 68159, Germany

Location

Somni Bene GmbH - Institut für Medizinische Forschung und Schlafmedizin

Schwerin, Germany

Location

Department of Child and Adolescent Psychiatry

Dublin, 12, Ireland

Location

IRCCS Stella Maris - U.O. Psichiatria e Psicofarmacologia Eta' Evolutiva

Pisa, 56018, Italy

Location

Università Cattolica del Sacro Cuore

Rome, 00168, Italy

Location

Ospedale Policlinico G.B.Rossi - Azienda Ospedaliera Universitaria Integrata Verona

Verona, 37134, Italy

Location

Indywidualna Specjalistyczna Praktyka Lekarska Borys Gniot

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

Centrum Neuropsychiatrii Neuromed

Wroclaw, Lower Silesian Voivodeship, 54-235, Poland

Location

Samodzielny Publiczny Dzieciecy Szpital Kliniczny

Warsaw, Masovian Voivodeship, 00-576, Poland

Location

Centrum Badan Klinicznych PI-House Sp. z o.o.

Gdansk, Pomeranian Voivodeship, 80-546, Poland

Location

NZOZ Gdan Skie Centrum Zdrowia

Gdansk, 80-542, Poland

Location

Gabinet Psychiatrii Doroslych, Dzieci i Mlodziezy, Miroslaw Dabkowski

Torun, 87-100, Poland

Location

Spitalul Clinic de Urgenta Pentru Copii Cluj

Cluj-Napoca, Cluj, 400660, Romania

Location

Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu"

Timișoara, Timiș County, 300239, Romania

Location

Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia"

Bucharest, Romania

Location

Spitalul Clinic de Psihiatrie Socola

Iași, Romania

Location

Mutua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Policlínica Guipuzkoa

Donostia / San Sebastian, 20009, Spain

Location

Hospital Marítimo, (USMI-J)

Málaga, 29620, Spain

Location

Hospital de Dia Infantil y Juvenil Dr Diego Guigou y Costa

Santa Cruz de Tenerife, 38003, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39011, Spain

Location

Instituto Valenciano de Neurología Pediatrica

Valencia, 46010, Spain

Location

Drottning Silvias Barnsjukhus

Gothenburg, 411 18, Sweden

Location

Barn och Ungdomsmedicin klinik Mölnlycke

Mölnlycke, 43530, Sweden

Location

BUP mottagningen Varberg

Varberg, 432 43, Sweden

Location

Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine

Kharkiv, Kharkivs’ka Oblast’, 61068, Ukraine

Location

Regional Clinical Psychiatric Hospital

Donetsk, 83037, Ukraine

Location

Municipal Institution "Institute of healthcare for children and adolescences NAMNU

Kharkiv, 61153, Ukraine

Location

Kherson Regional Psychiatric Hospital

Kherson, 73488, Ukraine

Location

Lviv Regional Clinical Psychiatric Hospital

Lviv, 79021, Ukraine

Location

Odesa Regional Psychoneurological Dispensary, Outpatient Dept

Odesa, 65084, Ukraine

Location

O.F. Maltsev Poltava Regional Psychiatric Hospital

Poltava, 36000, Ukraine

Location

Vinnytsia National Medical University - Vinnytsia Regional Psycho-Neurological Hospital

Vinnytsia, 21005, Ukraine

Location

Victoria Hospital

Kirkcaldy, Fife, KY2 5AH, United Kingdom

Location

James Paget University Hospital NHS Trust

Great Yarmouth, Norfolk, NR31 6SQ, United Kingdom

Location

Ashurt Child and Family Centre

Ashurst, Southampton, SO40 7AR, United Kingdom

Location

Horsham Child and Adolescent Mental Health Services

Horsham, United Kingdom

Location

5 Boroughs Partnership NHS Trust

Wigan, WN2 2JA, United Kingdom

Location

Related Publications (1)

• Hervas A, Huss M, Johnson M, McNicholas F, van Stralen J, Sreckovic S, Lyne A, Bloomfield R, Sikirica V, Robertson B. Efficacy and safety of extended-release guanfacine hydrochloride in children and adolescents with attention-deficit/hyperactivity disorder: a randomized, controlled, phase III trial. Eur Neuropsychopharmacol. 2014 Dec;24(12):1861-72. doi: 10.1016/j.euroneuro.2014.09.014. Epub 2014 Oct 23.

  PMID: 25453486 RESULT

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Guanfacine; Atomoxetine Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Propylamines; Amines

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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2010
• First Posted: November 19, 2010
• Study Start: January 17, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: July 2, 2021
• Results First Posted: July 14, 2014

Record last verified: 2021-06

Locations

PL (6); DE (11); AU (2); IT (3); RO (4); IE (1); SE (3); US (11); FR (3); CA (2); ES (7); UA (8); GB (5)