Clinical trial NCT01081145: Maintenance of Efficacy of Extended-Release Guanfacine HCl in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD)
Official title: A Phase 3, Double-blind, Placebo-controlled, Multicentre, Randomised Withdrawal, Long-term Maintenance of Efficacy and Safety Study of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 With Attention Deficit/Hyperactivity Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Attention-deficit/Hyperactivity Disorder
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-03-05
Enrollment: 528
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: 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.


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.

Primary outcomes:
measure: Percentage of Participants With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase
timeFrame: 26 weeks
Secondary outcomes:
measure: Time to Treatment Failure During the Double-Blind Randomized-Withdrawal Phase
timeFrame: 26 weeks
measure: 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)
timeFrame: Baseline and week 26
measure: 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
timeFrame: 26 weeks
measure: 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
timeFrame: Baseline and week 26
measure: Health Utilities Index-2/3 (HUI 2/3) Scores During the Double-Blind Randomized-Withdrawal Phase - LOCF
timeFrame: 26 weeks
measure: Columbia-Suicide Severity Rating Scale During Double-Blind Randomized-Withdrawal Phase
timeFrame: 26 weeks
measure: Change From Open-Label Baseline in ADHD-RS-IV Total Score at Week 13 of the Open-Label Phase - LOCF
timeFrame: Baseline and 13 weeks
measure: Percentage of Responders in the Open-Label Phase - LOCF
timeFrame: 13 weeks
measure: Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores During Open-Label Phase - LOCF
timeFrame: 13 weeks
measure: Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on CGI-S Scale During the Open-Label Phase - LOCF
timeFrame: 13 weeks
measure: Change From Open-Label Baseline in WFIRS-P Global Score at Week 13 of the Open-Label Phase - LOCF
timeFrame: Baseline and week 13
measure: HUI 2/3 Scores During the Open-Label Phase - LOCF
timeFrame: 13 weeks
measure: Columbia-Suicide Severity Rating Scale During Open-Label Phase
timeFrame: 13 weeks
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Harmonex Neuroscience Research
state: Alabama
city: Little Rock
country: United States
facility: Clinical Study Centers, LLC
state: Arkansas
city: San Diego
country: United States
facility: Psychiatric Centers at San Diego, Feighner Research
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research - North Coast
state: California
city: Wildomar
country: United States
facility: Elite Clinical Trials, Inc.
state: California
city: Bradenton
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Hialeah
country: United States
facility: Amedica Research Institute, Inc.
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Maitland
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Naperville
country: United States
facility: AMR-Baber Research Inc.
state: Illinois
city: Indianapolis
country: United States
facility: Goldpoint Clinical Research, LLC
state: Indiana
city: New Orleans
country: United States
facility: Louisiana Research Associates, Inc.
state: Louisiana
city: Salisbury
country: United States
facility: Delmarva Family Resources
state: Maryland
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine, Inc.
state: Nevada
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Durham
country: United States
facility: Triangle Neuropsychiatry, PLLC
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University, Nisonger Center
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Salem
country: United States
facility: Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)
state: Oregon
city: Philadelphia
country: United States
facility: CRI Worldwide, LLC
state: Pennsylvania
city: Austin
country: United States
facility: FutureSearch Clinical Trials
state: Texas
city: San Antonio
country: United States
facility: ADHD Clinic of San Antonio
state: Texas
city: Richmond
country: United States
facility: Alliance Research Group, LLC
state: Virginia
city: Kirkland
country: United States
facility: Eastside Therapeutic Resource
state: Washington
city: Hoboken
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen
state: Antwerpen
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
state: Brussels
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-vlaanderen
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Ham
country: Belgium
facility: Huisartspraktijk Jaak Mortelmans
city: Namur
country: Belgium
facility: Centre de référence Neuropédiatrique Multidisciplinaire
city: Uccle
country: Belgium
facility: Psypluriel
city: Vlezenbeek
country: Belgium
facility: Ziekenhuis Inkendaal Koninklijke Instelling v.z.w.
city: Vancouver
country: Canada
facility: Children's and Women's Health Centre of British Columbia
state: British Columbia
city: Ottawa
country: Canada
facility: JPM van Stralen Medicine Professional Corporation
state: Ontario
city: Whitby
country: Canada
facility: ADHD Clinic/The Kid's Clinic
state: Ontario
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Rouffach
country: France
facility: Centre Hospitalier de Rouffach
state: Alsace
city: Montpellier Cedex 5
country: France
facility: Hôpital Gui de Chauliac
state: Languedoc-roussillon
city: Amiens Cedex
country: France
facility: Centre Hospitalier Universitaire d'Amiens, Hôpital Nord
state: Picardie
city: Nice
country: France
facility: Hopitaux Pediatriques de Nice - CHI Lenval
state: Provcence Alpes Cote D'Azur
city: Dijon Cedex
country: France
facility: Centre Hospitalier Universitaire Bocage-Hôpital d'enfants
city: Paris cedex 19
country: France
facility: Hopital Robert-Debre'
city: Paris
country: France
facility: Hopital Robert Debre Centre pediatrique des pathologies du sommeil
city: Tours
country: France
facility: Hopital Gatien de Clocheville CHU de Tours
city: Tübingen
country: Germany
facility: Center for Pediatric Clinical Studies
state: Baden-wuerttemberg
city: Ulm
country: Germany
facility: Universitätsklinik Ulm
state: Baden-wuerttemberg
city: München
country: Germany
facility: Praxis Dr. med. Dipl. Psych. Anton Lindermüller
state: Bayern
city: Wurzburg
country: Germany
facility: Medizinisches Studienzentrum Wurzburg
state: Bayern
city: Dorsten
country: Germany
facility: Sozialpsychiatrisches Centrum Dr. med. Ralph Meyers
state: Nordrhein-westfalen
city: Mainz
country: Germany
facility: Klinikum der Johannes-Gutenberg-Universität Mainz
state: Rheinland-pfalz
city: Jena
country: Germany
facility: Friedrich-Schiller-Universitat Jena
state: Thuringen
city: Berlin
country: Germany
facility: Emovis GmbH
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Rho
country: Italy
facility: Azienda Ospedaliera "Guido Salvini"
state: Milan
city: Calambrone
country: Italy
facility: IRCCS Fondazione Stella Maris
state: Pisa
city: Catania
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico-Vittorio
city: Milano
country: Italy
facility: Azienda Osp. Fatebenefratelli - Polo Territoriale UONPIA
city: Padova
country: Italy
facility: Azienda ULSS 16 Padova
city: Roma
country: Italy
facility: Drottning Silvias Barnsjukhus
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Almere
country: Netherlands
facility: FlevoResearch
state: Flevoland
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
state: Limburg
city: Maastricht
country: Netherlands
facility: Mondriaan Zorggroep Heerlen, Kinder en Jeugdp sychiatrie
city: Donostia-San Sebastián
country: Spain
facility: Policlínica Guipuzkoa
state: Guipuzcoa
city: Palma
country: Spain
facility: Hospital Son Llàtzer, Laboratorio de Neurociencias IUNICS
state: Islas Baleares
city: Alcorcon
country: Spain
facility: Hospital Fundacion Alcorcon
state: Madrid
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Infanta Leonor
city: Valencia
country: Spain
facility: Instituto Valenciano de Neurología Pediatrica
city: Mölnlycke
country: Sweden
facility: Barn och Ungdomsmedicin klinik Mölnlycke
city: Norwich
country: United Kingdom
facility: Norfolk Community Health and Care NHS Trust
state: England
city: Sheffield
country: United Kingdom
facility: Ryegate Children's Centre
state: England
city: Sheffield
country: United Kingdom
facility: Centenary House Child and Adolescent Mental Health Services
state: England
city: Welwyn Garden City
country: United Kingdom
facility: Queen Elizabeth II Hospital
state: England
city: Grays
country: United Kingdom
facility: Thurrock Community Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: Stevenage
country: United Kingdom
facility: Lister Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.