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

NCT ID: NCT01244490

Last Updated: 2021-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 338 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-17
• Study Completion Date: 2013-05-01

Brief Summary

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

Conditions

Attention Deficit Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Extended-release Guanfacine Hydrochloride

Group Type: EXPERIMENTAL

Extended-release Guanfacine Hydrochloride

Intervention Type: DRUG

Tablet, once daily, optimised dose (1mg to 7mg based on age and weight), 6-week maintenance duration on optimised dose.

Atomoxetine Hydrochloride

Active Reference

Group Type: OTHER

Atomoxetine Hydrochloride

Intervention Type: DRUG

Capsule, once daily, optimised dose (10mg to 100mg based on weight), 8-9-weeks maintenance duration on optimised dose

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo Comparator

Intervention Type: DRUG

Placebo

Interventions

Extended-release Guanfacine Hydrochloride

Tablet, once daily, optimised dose (1mg to 7mg based on age and weight), 6-week maintenance duration on optimised dose.

Intervention Type: DRUG

Atomoxetine Hydrochloride

Capsule, once daily, optimised dose (10mg to 100mg based on weight), 8-9-weeks maintenance duration on optimised dose

Intervention Type: DRUG

Placebo Comparator

Placebo

Intervention Type: DRUG

Other Intervention Names

Intuniv; Strattera

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Psychiatric Centers at San Diego, Feighner Research

San Diego, California, United States

Florida Clinical Research Center, LLC

Maitland, Florida, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

Psychiatric Associates

Overland Park, Kansas, United States

Rochester Center for Behavioral Medicine

Rochester Hills, Michigan, United States

University of Nebraska Medical Center, Dept. of Psychiatry

Omaha, Nebraska, United States

Innovis Health

Fargo, North Dakota, United States

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, United States

Claghorn-Lesem Research Clinic

Houston, Texas, United States

R/D Clincial Research, Inc.

Lake Jackson, Texas, United States

NeuroScience Inc.

Herndon, Virginia, United States

Medizinische Universitat Graz-Universitaklinik fur Kinder-und Jugendheilkunde

Graz, , Austria

Institut für Psychosomatik

Vienna, , Austria

Dr Grazyna B. Jackiewicz, MD

Niagara Falls, Ontario, Canada

JPM Van Stralen Medicine Professional Corp.

Ottawa, Ontario, Canada

Centre HospitalierUniversitaire d'Amiens, Hoptial Nord

Amiens, Picardie, France

Centre Hospitalier Charles Perens - Service de Psychiatrie de l'Enfant et de l'Adolescent

Bordeaux, , France

Centre Hospitalier des Pyrenees

Chartres, , France

Praxis Dr. Wolff

Hagen, North Rhine-Westphalia, Germany

Praxis Dr. Andreas Mahler

Achim, , Germany

Emovis GmbH

Berlin, , Germany

Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden

Dresden, , Germany

Praxisgemeinschaft Drs. Willem Geraets/Gabriele Lucassen

Düsseldorf, , Germany

Praxis Dr. Walter Robert Otto

Fulda, , Germany

Praxis Dr. Friedrich Kaiser un Ingrid Marinesse

Hamburg, , Germany

Institut fur Ganzheitiche Medzin und Wissenschaft GmbH

Hüttenberg, , Germany

Klinikum der Johannes-Guttenberg-Universitat Mainz

Mainz, , Germany

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

Mannheim, , Germany

Somni Bene GmbH - Institut für Medizinische Forschung und Schlafmedizin

Schwerin, , Germany

Department of Child and Adolescent Psychiatry

Dublin, , Ireland

IRCCS Stella Maris - U.O. Psichiatria e Psicofarmacologia Eta' Evolutiva

Pisa, , Italy

Università Cattolica del Sacro Cuore

Rome, , Italy

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

Verona, , Italy

Indywidualna Specjalistyczna Praktyka Lekarska Borys Gniot

Torun, Kuyavian-Pomeranian Voivodeship, Poland

Centrum Neuropsychiatrii Neuromed

Wroclaw, Lower Silesian Voivodeship, Poland

Samodzielny Publiczny Dzieciecy Szpital Kliniczny

Warsaw, Masovian Voivodeship, Poland

Centrum Badan Klinicznych PI-House Sp. z o.o.

Gdansk, Pomeranian Voivodeship, Poland

NZOZ Gdan Skie Centrum Zdrowia

Gdansk, , Poland

Gabinet Psychiatrii Doroslych, Dzieci i Mlodziezy, Miroslaw Dabkowski

Torun, , Poland

Spitalul Clinic de Urgenta Pentru Copii Cluj

Cluj-Napoca, Cluj, Romania

Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu"

Timișoara, Timiș County, Romania

Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia"

Bucharest, , Romania

Spitalul Clinic de Psihiatrie Socola

Iași, , Romania

Mutua de Terrassa

Terrassa, Barcelona, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Policlínica Guipuzkoa

Donostia / San Sebastian, , Spain

Hospital Marítimo, (USMI-J)

Málaga, , Spain

Hospital de Dia Infantil y Juvenil Dr Diego Guigou y Costa

Santa Cruz de Tenerife, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Instituto Valenciano de Neurología Pediatrica

Valencia, , Spain

Drottning Silvias Barnsjukhus

Gothenburg, , Sweden

Barn och Ungdomsmedicin klinik Mölnlycke

Mölnlycke, , Sweden

BUP mottagningen Varberg

Varberg, , Sweden

Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Regional Clinical Psychiatric Hospital

Donetsk, , Ukraine

Municipal Institution "Institute of healthcare for children and adolescences NAMNU

Kharkiv, , Ukraine

Kherson Regional Psychiatric Hospital

Kherson, , Ukraine

Lviv Regional Clinical Psychiatric Hospital

Lviv, , Ukraine

Odesa Regional Psychoneurological Dispensary, Outpatient Dept

Odesa, , Ukraine

O.F. Maltsev Poltava Regional Psychiatric Hospital

Poltava, , Ukraine

Vinnytsia National Medical University - Vinnytsia Regional Psycho-Neurological Hospital

Vinnytsia, , Ukraine

Victoria Hospital

Kirkcaldy, Fife, United Kingdom

James Paget University Hospital NHS Trust

Great Yarmouth, Norfolk, United Kingdom

Ashurt Child and Family Centre

Ashurst, Southampton, United Kingdom

Horsham Child and Adolescent Mental Health Services

Horsham, , United Kingdom

5 Boroughs Partnership NHS Trust

Wigan, , United Kingdom

Countries

United States; Austria; Canada; France; Germany; Ireland; Italy; Poland; Romania; Spain; Sweden; Ukraine; United Kingdom

References

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.

Reference Type: RESULT

PMID: 25453486 (View on PubMed)

Other Identifiers

2010-018579-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SPD503-316

Identifier Type: -

Identifier Source: org_study_id