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

Information source: Shire
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Attention Deficit Hyperactivity Disorder

Intervention: Extended-release Guanfacine Hydrochloride (Drug); Atomoxetine Hydrochloride (Drug); Placebo Comparator (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Shire


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

Clinical Details

Official title: A Phase 3, Randomised, Double-blind, Multicentre, Parallel-group, Placebo- and Active-reference, Dose-optimisation Efficacy and Safety Study of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hyperactivity Disorder

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: 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)

Secondary outcome:

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

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

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

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

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

Change From Baseline in the WFIRS-P Global Score at Week 10/13 - LOCF

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

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

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

Change From Baseline in the WFIRS-P Child Self-Concept Domain Score at Week 10/13 - LOCF

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

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

Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Weeks 10/13 - LOCF

Structure Side-Effect Questionnaire

Columbia-Suicide Severity Rating Scale (C-SSRS)


Minimum age: 6 Years. Maximum age: 17 Years. Gender(s): Both.


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) Guidance E6, and applicable regulations before completing any study related procedures at Screening (Visit 1). 3. 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).

4. Subject has a minimum ADHD-RS-IV total score of 32 at Baseline (Visit 2). 5. Subject has a minimum CGI-S score of 4 at Baseline (Visit 2). 6. Subject is functioning at an age-appropriate level intellectually, as judged by the Investigator. 7. Subject and parent/LAR understand, are willing, able, and likely to fully comply with the study procedures and restrictions defined in this protocol. 8. Subject is able to swallow intact tablets and capsules. 9. 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. 10. Subject has supine and standing blood pressure (BP) measurement within the 95th percentile for age, sex, and height Exclusion Criteria: 1. 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. 2. Subject is well-controlled on their current medication, with acceptable tolerability, and the parent/caregiver does not object to the current medication. 3. Subject has any condition or illness including a 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. Mild stable asthma treated without the use of beta-2 agonist is not exclusionary. 4. 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. 5. Subject has a known family history of sudden cardiac death, ventricular arrhythmia, or QT prolongation. 6. Subjects with orthostatic hypotension or a known history of hypertension. 7. Subject has glaucoma. 8. Subject has clinically significant ECG findings as judged by the Investigator with consideration of the central ECG laboratory's interpretation. 9. 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. 10. 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). 11. 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. 12. Subject has taken another investigational product within 30 days prior to Baseline (Visit 2). 13. 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. 14. 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). 15. 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. 16. Clinically important abnormality on drug and alcohol screen (excluding the subject's current ADHD stimulant if applicable) at Screening (Visit 1) 17. Subject is female and is pregnant or currently lactating. 18. Subject failed screening or was previously enrolled in this study. 19. 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 suicide ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the Investigator. 20. History of failure to respond to an adequate trial of an α2-agonist or atomoxetine hydrochloride for the treatment of ADHD (consisting of an appropriate dose and adequate duration of therapy in the opinion of the investigator). 21. Subjects with renal or hepatic insufficiency.

Locations and Contacts

Medizinische Universitat Graz-Universitaklinik fur Kinder-und Jugendheilkunde, Graz 8036, Austria

Institut für Psychosomatik, Wien 1010, Austria

Centre Hospitalier Charles Perens - Service de Psychiatrie de l'Enfant et de l'Adolescent, Bordeaux 33076, France

Centre Hospitalier des Pyrenees, Chartres 28018, France

Praxis Dr. Andreas Mahler, Achim 28832, Germany

Emovis GmbH, Berlin 10629, Germany

Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden, Dresden 01307, Germany

Praxisgemeinschaft Drs. Willem Geraets/Gabriele Lucassen, Dusseldorf 40215, Germany

Praxis Dr. Walter Robert Otto, Fulda 36037, Germany

Praxis Dr. Friedrich Kaiser un Ingrid Marinesse, Hamburg 22415, Germany

Institut fur Ganzheitiche Medzin und Wissenschaft GmbH, Huttenberg 35625, Germany

Klinikum der Johannes-Guttenberg-Universitat Mainz, Mainz 55131, Germany

Zentralinstitut fur Seelische Geseundheit Mannheim Klinik for Psuchiatrie und Psychotherapie des Kindes, Mannheim 68159, Germany

Somni Bene GmbH - Institut für Medizinische Forschung und Schlafmedizin, Schwerin, Germany

Department of Child and Adolescent Psychiatry, Dublin 12, Ireland

IRCCS Stella Maris - U.O. Psichiatria e Psicofarmacologia Eta' Evolutiva, Pisa 56018, Italy

Università Cattolica del Sacro Cuore, Rome 00168, Italy

Ospedale Policlinico G.B.Rossi - Azienda Ospedaliera Universitaria Integrata Verona, Verona 37134, Italy

NZOZ Gdan Skie Centrum Zdrowia, Gdansk 80-542, Poland

Gabinet Psychiatrii Doroslych, Dzieci i Mlodziezy, Miroslaw Dabkowski, Torun 87-100, Poland

Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia", Bucuresti, Romania

Spitalul Clinic de Psihiatrie Socola, Iasi, Romania

Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain

Policlínica Guipuzkoa, Donostia-San Sebastián 20009, Spain

Hospital Marítimo, (USMI-J), Malaga 29620, Spain

Hospital de Dia Infantil y Juvenil Dr Diego Guigou y Costa, Santa Cruz de Tenerife 38003, Spain

Hospital Universitario Marques de Valdecilla, Santander 39011, Spain

Instituto Valenciano de Neurología Pediatrica, Valencia 46010, Spain

Drottning Silvias Barnsjukhus, Goteborg 411 18, Sweden

Barn och Ungdomsmedicin klinik Mölnlycke, Mölnlycke 43530, Sweden

BUP mottagningen Varberg, Varberg 432 43, Sweden

Regional Clinical Psychiatric Hospital, Donetsk 83037, Ukraine

Municipal Institution "Institute of healthcare for children and adolescences NAMNU, Kharkiv 61153, Ukraine

Kherson Regional Psychiatric Hospital, Kherson 73488, Ukraine

Lviv Regional Clinical Psychiatric Hospital, Lviv 79021, Ukraine

Odesa Regional Psychoneurological Dispensary, Outpatient Dept, Odesa 65084, Ukraine

O.F. Maltsev Poltava Regional Psychiatric Hospital, Poltava 36000, Ukraine

Vinnytsia National Medical University - Vinnytsia Regional Psycho-Neurological Hospital, Vinnytsia 21005, Ukraine

Horsham Child and Adolescent Mental Health Services, Horsham, United Kingdom

5 Boroughs Partnership NHS Trust, Wigan WN2 2JA, United Kingdom

Mutua de Terrassa, Terrassa, Barcelona 08221, Spain

Psychiatric Centers at San Diego, Feighner Research, San Diego, California 92108, United States

Spitalul Clinic de Urgenta Pentru Copii Cluj, Cluj Napoca, Cluj 400660, Romania

Centrum Neuropsychiatrii Neuromed, Wroclaw, Dolnoslaskie 54-235, Poland

Victoria Hospital, Kirkcaldy, Fife KY2 5AH, United Kingdom

Florida Clinical Research Center, LLC, Maitland, Florida 32751, United States

Atlanta Center for Medical Research, Atlanta, Georgia 30308, United States

Psychiatric Associates, Overland Park, Kansas 66211, United States

Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine, Kharkov, Kharkiv 61068, Ukraine

Indywidualna Specjalistyczna Praktyka Lekarska Borys Gniot, Torun, Kujawsko-pomorskie 87-100, Poland

Samodzielny Publiczny Dzieciecy Szpital Kliniczny, Warszawa, Mazowieckie 00-576, Poland

Rochester Center for Behavioral Medicine, Rochester Hills, Michigan 48307, United States

University of Nebraska Medical Center, Dept. of Psychiatry, Omaha, Nebraska 68198-5581, United States

Praxis Dr. Wolff, Hagen, Nordrhein-Westfalen 58093, Germany

James Paget University Hospital NHS Trust, Great Yarmouth, Norfolk NR31 6SQ, United Kingdom

Innovis Health, Fargo, North Dakota 58103, United States

Dr Grazyna B. Jackiewicz, MD, Niagra Falls, Ontario L2E 6A4, Canada

JPM Van Stralen Medicine Professional Corp., Ottowa, Ontario K2G 1W2, Canada

Centre HospitalierUniversitaire d'Amiens, Hoptial Nord, Amiens Cedex, Picardie 80054, France

Centrum Badan Klinicznych PI-House Sp. z o.o., Gdansk, Pomorskie 80-546, Poland

Ashurt Child and Family Centre, Ashurst, Southampton SO40 7AR, United Kingdom

Clinical Neuroscience Solutions, Inc., Memphis, Tennessee 38119, United States

Claghorn-Lesem Research Clinic, Houston, Texas 77008, United States

R/D Clincial Research, Inc., Lake Jackson, Texas 77566, United States

Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu", Timisoara, Timis 300239, Romania

NeuroScience Inc., Herndon, Virginia 20170, United States

Additional Information

Starting date: January 2011
Last updated: February 4, 2015

Page last updated: August 23, 2015

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