Attention Deficit Hyperactivity DisorderPhase 3NCT01244490
Efficacy and Safety of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)
A Phase 3 study testing Extended-release Guanfacine Hydrochloride and Atomoxetine Hydrochloride in people with Attention Deficit Hyperactivity Disorder, run by Shire at 66 sites in 13 countries.
Trial summary
For children and adolescents, how does SPD503 compare to placebo for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- What is being tested?
- Extended-release Guanfacine Hydrochloride and Atomoxetine Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 338 participants
- Where
- 66 sitesin 13 countries
- Study dates
- 17 Jan 2011to 1 May 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
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- 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
Who cannot join
- 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 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.
- 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.
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- 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)
- 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 suicide ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the Investigator.
- 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).
- Subjects with renal or hepatic insufficiency.
Trial locations and contacts
66 sites in 13 countries.
66 sites in 13 countries
United States11 sites
Atlanta Center for Medical Research
Atlanta, Georgia, 30308
Innovis Health
Fargo, North Dakota, 58103
NeuroScience Inc.
Herndon, Virginia, 20170
Claghorn-Lesem Research Clinic
Houston, Texas, 77008
R/D Clincial Research, Inc.
Lake Jackson, Texas, 77566
Florida Clinical Research Center, LLC
Maitland, Florida, 32751
Clinical Neuroscience Solutions, Inc.
Memphis, Tennessee, 38119
University of Nebraska Medical Center, Dept. of Psychiatry
Omaha, Nebraska, 68198-5581
Psychiatric Associates
Overland Park, Kansas, 66211
Rochester Center for Behavioral Medicine
Rochester Hills, Michigan, 48307
Psychiatric Centers at San Diego, Feighner Research
San Diego, California, 92108
Germany11 sites
Praxis Dr. Andreas Mahler
Achim, 28832
Emovis GmbH
Berlin, 10629
Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden
Dresden, 01307
Praxisgemeinschaft Drs. Willem Geraets/Gabriele Lucassen
Düsseldorf, 40215
Praxis Dr. Walter Robert Otto
Fulda, 36037
Praxis Dr. Wolff
Hagen, North Rhine-Westphalia, 58093
Praxis Dr. Friedrich Kaiser un Ingrid Marinesse
Hamburg, 22415
Institut fur Ganzheitiche Medzin und Wissenschaft GmbH
Hüttenberg, 35625
Klinikum der Johannes-Guttenberg-Universitat Mainz
Mainz, 55131
Zentralinstitut fur Seelische Geseundheit Mannheim Klinik for Psuchiatrie und Psychotherapie des Kindes
Mannheim, 68159
Somni Bene GmbH - Institut für Medizinische Forschung und Schlafmedizin
Schwerin
Ukraine8 sites
Regional Clinical Psychiatric Hospital
Donetsk, 83037
Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine
Kharkiv, Kharkiv Oblast, 61068
Municipal Institution "Institute of healthcare for children and adolescences NAMNU
Kharkiv, 61153
Kherson Regional Psychiatric Hospital
Kherson, 73488
Lviv Regional Clinical Psychiatric Hospital
Lviv, 79021
Odesa Regional Psychoneurological Dispensary, Outpatient Dept
Odesa, 65084
O.F. Maltsev Poltava Regional Psychiatric Hospital
Poltava, 36000
Vinnytsia National Medical University - Vinnytsia Regional Psycho-Neurological Hospital
Vinnytsia, 21005
Spain7 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Policlínica Guipuzkoa
Donostia / San Sebastian, 20009
Hospital Marítimo, (USMI-J)
Málaga, 29620
Hospital de Dia Infantil y Juvenil Dr Diego Guigou y Costa
Santa Cruz de Tenerife, 38003
Hospital Universitario Marques de Valdecilla
Santander, 39011
Mutua de Terrassa
Terrassa, Barcelona, 08221
Instituto Valenciano de Neurología Pediatrica
Valencia, 46010
Poland6 sites
Centrum Badan Klinicznych PI-House Sp. z o.o.
Gdansk, Pomeranian Voivodeship, 80-546
NZOZ Gdan Skie Centrum Zdrowia
Gdansk, 80-542
Indywidualna Specjalistyczna Praktyka Lekarska Borys Gniot
Torun, Kuyavian-Pomeranian Voivodeship, 87-100
Gabinet Psychiatrii Doroslych, Dzieci i Mlodziezy, Miroslaw Dabkowski
Torun, 87-100
Samodzielny Publiczny Dzieciecy Szpital Kliniczny
Warsaw, Masovian Voivodeship, 00-576
Centrum Neuropsychiatrii Neuromed
Wroclaw, Lower Silesian Voivodeship, 54-235
United Kingdom5 sites
Ashurt Child and Family Centre
Ashurst, Southampton, SO40 7AR
James Paget University Hospital NHS Trust
Great Yarmouth, Norfolk, NR31 6SQ
Horsham Child and Adolescent Mental Health Services
Horsham
Victoria Hospital
Kirkcaldy, Fife, KY2 5AH
5 Boroughs Partnership NHS Trust
Wigan, WN2 2JA
Romania4 sites
Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia"
Bucharest
Spitalul Clinic de Urgenta Pentru Copii Cluj
Cluj-Napoca, Cluj, 400660
Spitalul Clinic de Psihiatrie Socola
Iași
Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu"
Timișoara, Timiș County, 300239
France3 sites
Centre HospitalierUniversitaire d'Amiens, Hoptial Nord
Amiens, Picardie, 80054
Centre Hospitalier Charles Perens - Service de Psychiatrie de l'Enfant et de l'Adolescent
Bordeaux, 33076
Centre Hospitalier des Pyrenees
Chartres, 28018
Italy3 sites
IRCCS Stella Maris - U.O. Psichiatria e Psicofarmacologia Eta' Evolutiva
Pisa, 56018
Università Cattolica del Sacro Cuore
Rome, 00168
Ospedale Policlinico G.B.Rossi - Azienda Ospedaliera Universitaria Integrata Verona
Verona, 37134
Sweden3 sites
Drottning Silvias Barnsjukhus
Gothenburg, 411 18
Barn och Ungdomsmedicin klinik Mölnlycke
Mölnlycke, 43530
BUP mottagningen Varberg
Varberg, 432 43
Austria2 sites
Medizinische Universitat Graz-Universitaklinik fur Kinder-und Jugendheilkunde
Graz, 8036
Institut für Psychosomatik
Vienna, 1010
Canada2 sites
Dr Grazyna B. Jackiewicz, MD
Niagara Falls, Ontario, L2E 6A4
JPM Van Stralen Medicine Professional Corp.
Ottawa, Ontario, K2G 1W2
About this study
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
For children and adolescents, how does SPD503 compare to placebo for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD).
- Conditions
- Attention Deficit Hyperactivity Disorder
- Being tested
- Extended-release Guanfacine Hydrochloride, Atomoxetine Hydrochloride, Placebo Comparator
- Keywords
- ADHD
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extended-release Guanfacine HydrochlorideDrug
Also called Intuniv
Tablet, once daily, optimised dose (1mg to 7mg based on age and weight), 6-week maintenance duration on optimised dose.
Atomoxetine HydrochlorideDrug
Also called Strattera
Capsule, once daily, optimised dose (10mg to 100mg based on weight), 8-9-weeks maintenance duration on optimised dose
Placebo ComparatorDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Extended-release Guanfacine Hydrochloride | Experimental | Not described Receives: Drug: Extended-release Guanfacine Hydrochloride |
| Atomoxetine Hydrochloride | Other | Active Reference Receives: Drug: Atomoxetine Hydrochloride |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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
The WFIRS-P Learning in School Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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
The WFIRS-P Family Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill). Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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
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. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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 Global Score at Week 10/13 - LOCF
The WFIRS-P Global Score is the mean of 50 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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 Academic Performance Domain Score at Week 10/13 - LOCF
The WFIRS-P Academic Performance Domain is the mean of 4 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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 Behavior in School Domain Score at Week 10/13 - LOCF
The WFIRS-P Behavior in School Domain is the mean of 6 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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 Life Skills Domain Score at Week 10/13 - LOCF
The WFIRS-P Life Skills Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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 Child Self-Concept Domain Score at Week 10/13 - LOCF
The WFIRS-P Child Self-Concept Domain is the mean of 3 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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 Social Domain Score at Week 10/13 - LOCF
The WFIRS-P Social Domain is the mean of 7 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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 Risk Domain Score at Week 10/13 - LOCF
The WFIRS-P Risk Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: 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 Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Weeks 10/13 - LOCF
The BPRS-C characterizes childhood behavioral and emotional symptomatology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.
Measured: Baseline and up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
Structure Side-Effect Questionnaire
The Structured Side-effect Questionnaire is a simple checklist of 17 side effects. The subject indicates whether a side effect has occurred since the last visit by marking 'yes' on the checklist for each of the events listed. Outcome measure is at 12 weeks for ages 6-12 years and at 15 weeks for ages 13-17 years.
Measured: Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years
Columbia-Suicide Severity Rating Scale (C-SSRS)
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. Outcome measure is at 12 weeks for ages 6-12 years and at 15 weeks for ages 13-17 years.
Measured: Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2010 (estimated)
- Study start17 Jan 2011
- Primary completion1 May 2013
- Study completion1 May 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit Hyperactivity DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 338 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01244490
- Sponsor's protocol ID
- SPD503-316
- Other IDs
- 2010-018579-12
- Status last verified
- Jun 2021
- First submitted
- 16 Nov 2010
- Last updated
- 2 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 25453486
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01244490
- Acronym / sponsor ID
- SPD503-316
- Conditions
- Attention Deficit Hyperactivity Disorder
- Keywords
- ADHD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 338 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 17 Jan 2011 (actual)
- Primary completion
- 1 May 2013 (actual)
- Study completion
- 1 May 2013 (actual)
- First posted
- 19 Nov 2010 (estimated)
- Results
- Posted 14 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
For children and adolescents, how does SPD503 compare to placebo for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Extended-release Guanfacine Hydrochloride | Experimental | Drug: Extended-release Guanfacine Hydrochloride |
| Atomoxetine Hydrochloride | Other | Drug: Atomoxetine HydrochlorideActive Reference |
| Placebo | Placebo comparator | Drug: Placebo Comparator |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (21 listed)
- 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 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Extended-release Guanfacine HydrochlorideAlso: IntunivTablet, once daily, optimised dose (1mg to 7mg based on age and weight), 6-week maintenance duration on optimised dose. | Drug | Extended-release Guanfacine Hydrochloride |
| Atomoxetine HydrochlorideAlso: StratteraCapsule, once daily, optimised dose (10mg to 100mg based on weight), 8-9-weeks maintenance duration on optimised dose | Drug | Atomoxetine Hydrochloride |
| Placebo ComparatorPlacebo | Drug | Placebo |
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)
Time frame: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
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.
15 secondary outcomes
Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 Global Score at Week 10/13 - LOCF
Time frame: 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 Academic Performance Domain Score at Week 10/13 - LOCF
Time frame: 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 Behavior in School Domain Score at Week 10/13 - LOCF
Time frame: 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 Life Skills Domain Score at Week 10/13 - LOCF
Time frame: 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 Child Self-Concept Domain Score at Week 10/13 - LOCF
Time frame: 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 Social Domain Score at Week 10/13 - LOCF
Time frame: 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 Risk Domain Score at Week 10/13 - LOCF
Time frame: 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 Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Weeks 10/13 - LOCF
Time frame: Baseline and up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
Structure Side-Effect Questionnaire
Time frame: Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years
Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25453486Hervas 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
66 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Extended-release Guanfacine Hydrochloride and Atomoxetine Hydrochloride in people with Attention Deficit Hyperactivity Disorder, run by Shire at 66 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 66 sites in United States, Germany, Ukraine, Spain, Poland and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01244490, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2021.