Clinical trial NCT01244490: Efficacy and Safety of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Attention Deficit Hyperactivity Disorder
Keywords: ADHD
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-11-19
Enrollment: 338
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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) 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.

Primary outcomes:
measure: 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)
timeFrame: 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:
measure: Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores
timeFrame: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Learning and School Domain Scores at Week 10/13 - LOCF
timeFrame: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Change From Baseline in the WFIRS-P Family Domain Score at Week 10/13 - LOCF
timeFrame: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Clinical Global Impression-Severity of Illness (CGI-S) - LOCF
timeFrame: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Health Utilities Index-2/3 (HUI 2/3) Scores - LOCF
timeFrame: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Change From Baseline in the WFIRS-P Global Score at Week 10/13 - LOCF
timeFrame: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Change From Baseline in the WFIRS-P Academic Performance Domain Score at Week 10/13 - LOCF
timeFrame: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Change From Baseline in the WFIRS-P Behavior in School Domain Score at Week 10/13 - LOCF
timeFrame: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Change From Baseline in the WFIRS-P Life Skills Domain Score at Week 10/13 - LOCF
timeFrame: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Change From Baseline in the WFIRS-P Child Self-Concept Domain Score at Week 10/13 - LOCF
timeFrame: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Change From Baseline in the WFIRS-P Social Domain Score at Week 10/13 - LOCF
timeFrame: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Change From Baseline in the WFIRS-P Risk Domain Score at Week 10/13 - LOCF
timeFrame: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Weeks 10/13 - LOCF
timeFrame: Baseline and up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
measure: Structure Side-Effect Questionnaire
timeFrame: Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years
measure: Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Psychiatric Centers at San Diego, Feighner Research
state: California
city: Maitland
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Overland Park
country: United States
facility: Psychiatric Associates
state: Kansas
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center, Dept. of Psychiatry
state: Nebraska
city: Fargo
country: United States
facility: Innovis Health
state: North Dakota
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Tennessee
city: Houston
country: United States
facility: Claghorn-Lesem Research Clinic
state: Texas
city: Lake Jackson
country: United States
facility: R/D Clincial Research, Inc.
state: Texas
city: Herndon
country: United States
facility: NeuroScience Inc.
state: Virginia
city: Graz
country: Austria
facility: Medizinische Universitat Graz-Universitaklinik fur Kinder-und Jugendheilkunde
city: Wien
country: Austria
facility: Institut für Psychosomatik
city: Niagara Falls
country: Canada
facility: Dr Grazyna B. Jackiewicz, MD
state: Ontario
city: Ottawa
country: Canada
facility: JPM Van Stralen Medicine Professional Corp.
state: Ontario
city: Amiens Cedex
country: France
facility: Centre HospitalierUniversitaire d'Amiens, Hoptial Nord
state: Picardie
city: Bordeaux
country: France
facility: Centre Hospitalier Charles Perens - Service de Psychiatrie de l'Enfant et de l'Adolescent
city: Chartres
country: France
facility: Centre Hospitalier des Pyrenees
city: Hagen
country: Germany
facility: Praxis Dr. Wolff
state: Nordrhein-Westfalen
city: Achim
country: Germany
facility: Praxis Dr. Andreas Mahler
city: Berlin
country: Germany
facility: Emovis GmbH
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden
city: Dusseldorf
country: Germany
facility: Praxisgemeinschaft Drs. Willem Geraets/Gabriele Lucassen
city: Fulda
country: Germany
facility: Praxis Dr. Walter Robert Otto
city: Hamburg
country: Germany
facility: Praxis Dr. Friedrich Kaiser un Ingrid Marinesse
city: Huttenberg
country: Germany
facility: Institut fur Ganzheitiche Medzin und Wissenschaft GmbH
city: Mainz
country: Germany
facility: Klinikum der Johannes-Guttenberg-Universitat Mainz
city: Mannheim
country: Germany
facility: Zentralinstitut fur Seelische Geseundheit Mannheim Klinik for Psuchiatrie und Psychotherapie des Kindes
city: Schwerin
country: Germany
facility: Somni Bene GmbH - Institut für Medizinische Forschung und Schlafmedizin
city: Dublin
country: Ireland
facility: Department of Child and Adolescent Psychiatry
city: Pisa
country: Italy
facility: IRCCS Stella Maris - U.O. Psichiatria e Psicofarmacologia Eta' Evolutiva
city: Rome
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Verona
country: Italy
facility: Ospedale Policlinico G.B.Rossi - Azienda Ospedaliera Universitaria Integrata Verona
city: Wroclaw
country: Poland
facility: Centrum Neuropsychiatrii Neuromed
state: Dolnoslaskie
city: Torun
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska Borys Gniot
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Dzieciecy Szpital Kliniczny
state: Mazowieckie
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI-House Sp. z o.o.
state: Pomorskie
city: Gdansk
country: Poland
facility: NZOZ Gdan Skie Centrum Zdrowia
city: Torun
country: Poland
facility: Gabinet Psychiatrii Doroslych, Dzieci i Mlodziezy, Miroslaw Dabkowski
city: Cluj Napoca
country: Romania
facility: Spitalul Clinic de Urgenta Pentru Copii Cluj
state: Cluj
city: Timisoara
country: Romania
facility: Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu"
state: Timis
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia"
city: Iasi
country: Romania
facility: Spitalul Clinic de Psihiatrie Socola
city: Terrassa
country: Spain
facility: Mutua de Terrassa
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Donostia-San Sebastián
country: Spain
facility: Policlínica Guipuzkoa
city: Malaga
country: Spain
facility: Hospital Marítimo, (USMI-J)
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital de Dia Infantil y Juvenil Dr Diego Guigou y Costa
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valencia
country: Spain
facility: Instituto Valenciano de Neurología Pediatrica
city: Goteborg
country: Sweden
facility: Drottning Silvias Barnsjukhus
city: Mölnlycke
country: Sweden
facility: Barn och Ungdomsmedicin klinik Mölnlycke
city: Varberg
country: Sweden
facility: BUP mottagningen Varberg
city: Kharkov
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine
state: Kharkiv
city: Donetsk
country: Ukraine
facility: Regional Clinical Psychiatric Hospital
city: Kharkiv
country: Ukraine
facility: Municipal Institution "Institute of healthcare for children and adolescences NAMNU
city: Kherson
country: Ukraine
facility: Kherson Regional Psychiatric Hospital
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Psychiatric Hospital
city: Odesa
country: Ukraine
facility: Odesa Regional Psychoneurological Dispensary, Outpatient Dept
city: Poltava
country: Ukraine
facility: O.F. Maltsev Poltava Regional Psychiatric Hospital
city: Vinnytsia
country: Ukraine
facility: Vinnytsia National Medical University - Vinnytsia Regional Psycho-Neurological Hospital
city: Kirkcaldy
country: United Kingdom
facility: Victoria Hospital
state: Fife
city: Great Yarmouth
country: United Kingdom
facility: James Paget University Hospital NHS Trust
state: Norfolk
city: Ashurst
country: United Kingdom
facility: Ashurt Child and Family Centre
state: Southampton
city: Horsham
country: United Kingdom
facility: Horsham Child and Adolescent Mental Health Services
city: Wigan
country: United Kingdom
facility: 5 Boroughs Partnership NHS Trust
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.