Maintenance of Efficacy of Extended-Release Guanfacine HCl in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD)
- Conditions
- Attention-deficit/Hyperactivity Disorder
- Interventions
- Other: Placebo
- Registration Number
- NCT01081145
- Lead Sponsor
- Shire
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 528
- 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.
- 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).
- 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).
- 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).
- Subject has another member of the same household currently participating in this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Extended-release Guanfacine HCl Extended-release Guanfacine Hydrochloride - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase 26 weeks 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.
- Secondary Outcome Measures
Name Time Method 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 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.
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 CGI-S assesses the severity of the subject's condition on a 7-point scale: 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill)
Columbia-Suicide Severity Rating Scale During Double-Blind Randomized-Withdrawal Phase 26 weeks C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.
Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores During Open-Label Phase - LOCF 13 weeks Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Time to Treatment Failure During the Double-Blind Randomized-Withdrawal Phase 26 weeks 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.
Health Utilities Index-2/3 (HUI 2/3) Scores During the Double-Blind Randomized-Withdrawal Phase - LOCF 26 weeks HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.
Change From Open-Label Baseline in ADHD-RS-IV Total Score at Week 13 of the Open-Label Phase - LOCF Baseline and 13 weeks 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.
Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on CGI-S Scale During the Open-Label Phase - LOCF 13 weeks CGI-S assesses the severity of the subject's condition on a 7-point scale: 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill)
Change From Open-Label Baseline in WFIRS-P Global Score at Week 13 of the Open-Label Phase - LOCF Baseline and week 13 The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.
HUI 2/3 Scores During the Open-Label Phase - LOCF 13 weeks HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.
Columbia-Suicide Severity Rating Scale During Open-Label Phase 13 weeks C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.
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 The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.
Percentage of Responders in the Open-Label Phase - LOCF 13 weeks Response is defined as a percentage decrease (improvement) from Baseline in the ADHD-RS-IV total score of \>=30% and a CGI-S score of 1 or 2.
Trial Locations
- Locations (79)
Harmonex Neuroscience Research
🇺🇸Dothan, Alabama, United States
Amedica Research Institute, Inc.
🇺🇸Hialeah, Florida, United States
Ohio State University, Nisonger Center
🇺🇸Columbus, Ohio, United States
Goldpoint Clinical Research, LLC
🇺🇸Indianapolis, Indiana, United States
Psychiatric Centers at San Diego, Feighner Research
🇺🇸San Diego, California, United States
Triangle Neuropsychiatry, PLLC
🇺🇸Durham, North Carolina, United States
IPS Research Company
🇺🇸Oklahoma City, Oklahoma, United States
Children's and Women's Health Centre of British Columbia
🇨🇦Vancouver, British Columbia, Canada
Hospital Son Llàtzer, Laboratorio de Neurociencias IUNICS
🇪🇸Palma, Islas Baleares, Spain
Universitair Ziekenhuis Brussel
🇧🇪Jette, Brussels, Belgium
Ziekenhuis Netwerk Antwerpen
🇧🇪Hoboken, Antwerpen, Belgium
Psypluriel
🇧🇪Uccle, Belgium
Ziekenhuis Inkendaal Koninklijke Instelling v.z.w.
🇧🇪Vlezenbeek, Belgium
Norfolk Community Health and Care NHS Trust
🇬🇧Norwich, England, United Kingdom
Encompass Clinical Research - North Coast
🇺🇸Spring Valley, California, United States
Elite Clinical Trials, Inc.
🇺🇸Wildomar, California, United States
Clinical Study Centers, LLC
🇺🇸Little Rock, Arkansas, United States
Florida Clinical Research Center, LLC
🇺🇸Maitland, Florida, United States
AMR-Baber Research Inc.
🇺🇸Naperville, Illinois, United States
Delmarva Family Resources
🇺🇸Salisbury, Maryland, United States
Center for Psychiatry and Behavioral Medicine, Inc.
🇺🇸Las Vegas, Nevada, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
CRI Worldwide, LLC
🇺🇸Philadelphia, Pennsylvania, United States
Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)
🇺🇸Salem, Oregon, United States
ADHD Clinic of San Antonio
🇺🇸San Antonio, Texas, United States
Huisartspraktijk Jaak Mortelmans
🇧🇪Ham, Belgium
Universitair Ziekenhuis Gent
🇧🇪Ghent, Oost-vlaanderen, Belgium
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Belgium
Centre de référence Neuropédiatrique Multidisciplinaire
🇧🇪Namur, Belgium
ADHD Clinic/The Kid's Clinic
🇨🇦Whitby, Ontario, Canada
Royal University Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
Centre Hospitalier de Rouffach
🇫🇷Rouffach, Alsace, France
Hôpital Gui de Chauliac
🇫🇷Montpellier Cedex 5, Languedoc-roussillon, France
Centre Hospitalier Universitaire d'Amiens, Hôpital Nord
🇫🇷Amiens Cedex, Picardie, France
Hopitaux Pediatriques de Nice - CHI Lenval
🇫🇷Nice, Provcence Alpes Cote D'Azur, France
Centre Hospitalier Universitaire Bocage-Hôpital d'enfants
🇫🇷Dijon Cedex, France
Hopital Robert-Debre'
🇫🇷Paris cedex 19, France
Hopital Robert Debre Centre pediatrique des pathologies du sommeil
🇫🇷Paris, France
Hopital Gatien de Clocheville CHU de Tours
🇫🇷Tours, France
Center for Pediatric Clinical Studies
🇩🇪Tübingen, Baden-wuerttemberg, Germany
Universitätsklinik Ulm
🇩🇪Ulm, Baden-wuerttemberg, Germany
Praxis Dr. med. Dipl. Psych. Anton Lindermüller
🇩🇪München, Bayern, Germany
Sozialpsychiatrisches Centrum Dr. med. Ralph Meyers
🇩🇪Dorsten, Nordrhein-westfalen, Germany
Medizinisches Studienzentrum Wurzburg
🇩🇪Wurzburg, Bayern, Germany
Klinikum der Johannes-Gutenberg-Universität Mainz
🇩🇪Mainz, Rheinland-pfalz, Germany
Emovis GmbH
🇩🇪Berlin, Germany
Azienda Ospedaliera "Guido Salvini"
🇮🇹Rho, Milan, Italy
Universitatsklinikum Freiburg
🇩🇪Freiburg, Germany
IRCCS Fondazione Stella Maris
🇮🇹Calambrone, Pisa, Italy
Azienda Ospedaliero-Universitaria Policlinico-Vittorio
🇮🇹Catania, Italy
Azienda Osp. Fatebenefratelli - Polo Territoriale UONPIA
🇮🇹Milano, Italy
Azienda ULSS 16 Padova
🇮🇹Padova, Italy
FlevoResearch
🇳🇱Almere, Flevoland, Netherlands
Drottning Silvias Barnsjukhus
🇮🇹Roma, Italy
Università Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Mondriaan Zorggroep Heerlen, Kinder en Jeugdp sychiatrie
🇳🇱Maastricht, Netherlands
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Limburg, Netherlands
Hospital Fundacion Alcorcon
🇪🇸Alcorcon, Madrid, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Clínica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Infanta Leonor
🇪🇸Madrid, Spain
Barn och Ungdomsmedicin klinik Mölnlycke
🇸🇪Mölnlycke, Sweden
Instituto Valenciano de Neurología Pediatrica
🇪🇸Valencia, Spain
Ryegate Children's Centre
🇬🇧Sheffield, England, United Kingdom
Centenary House Child and Adolescent Mental Health Services
🇬🇧Sheffield, England, United Kingdom
Lister Hospital
🇬🇧Stevenage, United Kingdom
Queen Elizabeth II Hospital
🇬🇧Welwyn Garden City, England, United Kingdom
Thurrock Community Hospital
🇬🇧Grays, United Kingdom
Friedrich-Schiller-Universitat Jena
🇩🇪Jena, Thuringen, Germany
Policlínica Guipuzkoa
🇪🇸Donostia-San Sebastián, Guipuzcoa, Spain
Eastside Therapeutic Resource
🇺🇸Kirkland, Washington, United States
Sarkis Clinical Trials
🇺🇸Gainesville, Florida, United States
JPM van Stralen Medicine Professional Corporation
🇨🇦Ottawa, Ontario, Canada
Clinical Neuroscience Solutions, Inc.
🇺🇸Orlando, Florida, United States
Louisiana Research Associates, Inc.
🇺🇸New Orleans, Louisiana, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
FutureSearch Clinical Trials
🇺🇸Austin, Texas, United States
Alliance Research Group, LLC
🇺🇸Richmond, Virginia, United States
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom