Clinical trial NCT01500694: Access to Extended Release Guanfacine HCl for Subjects Who Participated in Studies SPD503-315 or SPD503-316 in Europe
Official title: A Phase 3, Open-label, Multicentre Study to Provide Access to Guanfacine Hydrochloride Extended-release for European Subjects With Attention-deficit/Hyperactivity Disorder (ADHD) Who Participated in Study SPD503-315 or SPD503-316
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-12-28
Enrollment: 215
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: For subjects in Europe that have already participated in either Study SPD503-315 or SPD503-316. This is an extension study that will allow participants access to Extended-release Guanfacine Hydrochloride (HCl) for up to 2 years. This study will help the sponsor evaluate long-term safety and tolerability of Extended-release Guanfacine HCl (SPD503).


Eligibility criteria: Inclusion Criteria:

1. Subjects where Study SPD503-318 was not available at the time of their final visit in the antecedent study (SPD503-315 or SPD503-316), may still be screened unless they are well-controlled on another ADHD medication with acceptable tolerability and the parent/caregiver is satisfied with their current ADHD medication.
2. Subject satisfied all entry criteria for the antecedent study (SPD503 315 or SPD503-316).
3. 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 the Screening Visit (Visit 1) and a negative urine pregnancy test at the Baseline Visit (Visit 2) and agree to comply with any applicable contraceptive requirements of the protocol.
4. 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 and applicable regulations, before completing any study-related procedures.
5. Subject and parent/LAR are willing, able, and likely to fully comply with all the testing and requirements defined in this protocol, including oversight of dosing. Specifically, the parent/LAR must be available upon awakening, to dispense the dose of investigational product for the duration of the study.
6. Subject has a supine and standing blood pressure (BP) measurement within the 95th percentile for age, sex, and height.
7. Subject is functioning at an age-appropriate level intellectually, as deemed by the Investigator.
8. Subject is able to swallow intact tablets.

Exclusion Criteria:

1. Subject has any current, controlled (requiring a prohibited medication or behavioural modification program) or uncontrolled, co-morbid psychiatric diagnosis (except oppositional defiant disorder), 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 treatment with SPD503 or confound efficacy or safety assessments. The Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime version (K-SADS-PL) rating from the antecedent study should be reviewed to confirm diagnosis, if necessary.
2. Subject who early terminated from Study SPD503-315 or Study SPD503-316 for protocol non-adherence, subject non-compliance, an AE, SAE, or withdrawal by subject.
3. Subject experienced any clinically significant AE in their prior SPD503 study (SPD503-315 or SPD503 316) that, in the opinion of the Investigator, would preclude exposure to SPD503.
4. Clinically important abnormality on urine drug and/or alcohol screen at the Screening Visit (Visit 1).
5. Subject has taken any investigational product as follows: last dose of investigational product in Study SPD503-315 within 7 days prior to the Baseline Visit (Visit 2); investigational product in Study SPD503 316 within 30 days prior to the Baseline Visit (Visit 2); any other investigational product within 30 days prior to the Baseline Visit (Visit 2) or any other ADHD medication within 30 days prior to Baseline Visit (Visit 2).
6. Subject is significantly overweight based on Center for Disease Control and Prevention Body Mass Index (BMI)-for-age sex-specific charts at the Screening Visit (Visit 1). Significantly overweight is defined as a BMI \>95th percentile.
7. Children aged 6 12 years with a body weight of less than 25.0kg or adolescents aged 13 years and older with a body weight of less than 34.0kg at the Screening Visit (Visit 1).
8. Subject has any condition or illness including clinically significant abnormal laboratory values at the Screening Visit (Visit 1) which, in the opinion of the Investigator, represents an inappropriate risk to the subject and/or could confound the interpretation of the study.
9. 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.
10. Subject has clinically significant ECG findings, as judged by the Investigator with consideration of the central ECG laboratory's interpretation, at the Baseline Visit (Visit 2).
11. Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride, or any components found in SPD503.
12. Subject has a history of alcohol or other substance abuse or dependence, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text RevisionÒ (DSM-IV-TRÒ; with the exception of nicotine) within the last 6 months.
13. 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.
14. Subject has a known history or presence of structural cardiac abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction problems (eg, clinically significant heart block), exercise related cardiac events including syncope and pre syncope, or clinically significant bradycardia.
15. Subject with orthostatic hypotension or a known history of controlled or uncontrolled hypertension.
16. Current use of any prohibited medication or other medications, including herbal supplements, that affect BP or heart rate or 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 the Baseline Visit (Visit 2).
17. Subject has a medical condition, other than ADHD, that requires treatment with medications that have CNS effects and/or affect performance.
18. Subject is female and is pregnant or currently lactating.
19. Subject failed screening or was previously enrolled in this study.

Primary outcomes:
measure: Change From Baseline in Mean Systolic Blood Pressure at Final Assessment
timeFrame: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)
measure: Change From Baseline in Mean Diastolic Blood Pressure at Final Assessment
timeFrame: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)
measure: Change From Baseline in Mean Supine Pulse at Final Assessment
timeFrame: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)
measure: Change From Baseline in Mean Height at Final Assessment
timeFrame: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)
measure: Change From Baseline in Mean Weight at Final Assessment
timeFrame: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)
measure: Change From Baseline in Electrocardiogram Result (QRS Interval) at Final Assessment
timeFrame: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)
measure: Change From Baseline in Electrocardiogram Result (QT Interval) at Final Assessment
timeFrame: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)
measure: Number of Participants With Suicidal Behavior and / or Ideation ("Yes" Response) on the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Final Assessment (last non missing data/up to Day 714)
Secondary outcomes:
measure: Change From Baseline in Attention-deficit and Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) - Total Score at Final Assessment
timeFrame: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)
measure: Number of Participants Assessed With Clinical Global Impression Severity of Illness (CGI-S) Scale
timeFrame: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medizinische Universitat Graz Univ fur Kinder
city: Wien
country: Austria
facility: Institut fur Psychosomatik
city: Hoboken
country: Belgium
facility: Universitaire Kinder-end Jeugdpsychatrie
city: Namur
country: Belgium
facility: Centre de Reference Neuropediatrique Multidisciplinaire
city: Oostham
country: Belgium
facility: Huisartspraktijk Jaak Mortelmans
city: Vlezenbeek
country: Belgium
facility: Zlekenhuis Inkendaal Koninklijke Instelling v.z.w.
city: Amiens Cedex
country: France
facility: Centre Hospitalier Universitaire Amiens
state: Picardie
city: Bordeaux Cedex
country: France
facility: Centre Hospitalier Charles Perrens
city: Montpellier
country: France
facility: Hopital Gui de Chauliac
city: Achim
country: Germany
facility: Dr. med. Andreas Mahler
city: Berlin
country: Germany
facility: Emovis GmbH
city: Dorsten
country: Germany
facility: Sozialpsychitrisches Zentrum
city: Dresden
country: Germany
facility: Klinik und Poliklinik fur Kinder-und Jugendpsychiatrie un psychotherapie
city: Fulda
country: Germany
facility: Dr. med Walter Robert Otto
city: Hagen
country: Germany
facility: Dr. med. Christian Wolff
city: Hamburg
country: Germany
facility: Dr. med Friedrich Kaiser
city: Huttenberg
country: Germany
facility: Institut fur Ganzheitliche Medizin und Wissenschaft GmbH
city: Jena
country: Germany
facility: Friedrich Schiller Universitat Jena Klinik fur Kinder und Jugendpsychiatrie
city: Mainz
country: Germany
facility: Universitatsmedizin der Johannes-Gutenberg-Universitat
city: Munchen
country: Germany
facility: Kinder-und Jugendpsychiatrische Praxis
city: Schwerin
country: Germany
facility: Somni bene GmbH Institut fur Medizinische Forschung und Schlatmedizin
city: Ulm
country: Germany
facility: Universitatsklinik Ulm
city: Crumlin
country: Ireland
facility: Our Lady's Children's Hospital
state: Dublin
city: Catania
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico-Vittorio
city: Milano
country: Italy
facility: Azienda Ospedallera G Salvini - Ospedale Di Circolo de RHO
city: Milano
country: Italy
facility: Azienda Ospedallera Fatebenefratelli
city: Padova
country: Italy
facility: U.O di Neuropsichiatria Infantile
city: Pisa
country: Italy
facility: IRCCS Fondazione Stella Maris
city: Verona
country: Italy
facility: Ospedale Policlinico GB Rossi
city: Almere
country: Netherlands
facility: Flevo Research
city: Heerlen
country: Netherlands
facility: Mondriaan Zorggroep
city: Gdansk
country: Poland
facility: NZOZ Gdanskie Centrum Zdrowia
city: Gdansk
country: Poland
facility: Centrum Badari Klinicznych House Sp. z.o.o.
city: Torun
country: Poland
facility: Gabinet Psychiatrii Doroslych, Dzieci i Mlodziezy
city: Torun
country: Poland
facility: Indywidualna Specjalisyczna Praktyka Lekarska
city: Wroclaw
country: Poland
facility: Contrum Neurospychiatrii Neuromed
city: Timisoara
country: Romania
facility: Spitalul Clinic de Urgenta pentru Copli
state: Timis
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Psihiatrie
city: Iasi
country: Romania
facility: Spitalul Clinic de Psihiatrie Socoia
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitani Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Infanta Leonor, Servicio de Psiquiatria
city: Madrid
country: Spain
facility: Hospital Fundacion Alcorcon
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
city: Santander
country: Spain
facility: Unidad de Salud Mental Infanto Juvenil
city: Valencia
country: Spain
facility: Instituto Valenciano de Neurologia Pediatrica
city: Goteborg
country: Sweden
facility: Drottning Silvias Barnsjukhus
city: Donetsk
country: Ukraine
facility: Regional Clinical Psychiatric Hospital
city: Kharkiv
country: Ukraine
facility: Institute of Health Care for Children and Teenagers
city: Kharkov
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Psychiatric Hospital
city: Odesa
country: Ukraine
facility: Odesa Regional Psychoneurological Dispensary
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Psychiatric Hospital
city: Vinnytsia
country: Ukraine
facility: Vinnitsya regional psychoneurological hospital
city: Stevenage
country: United Kingdom
facility: Lister Hospital
state: Herfordshire
city: Welwyn Garden City
country: United Kingdom
facility: Queen Elizabeth II Hospital - Howlands
state: Herfordshire
city: West Derby
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
state: Liverpool
city: Norwich
country: United Kingdom
facility: The Children's Centre
city: Sheffield
country: United Kingdom
facility: Ryegate Children's Centre
city: Sheffield
country: United Kingdom
facility: Centenary House Child and Adolescent Mental Health Services
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Huss M, Dirks B, Gu J, Robertson B, Newcorn JH, Ramos-Quiroga JA. Long-term safety and efficacy of guanfacine extended release in children and adolescents with ADHD. Eur Child Adolesc Psychiatry. 2018 Oct;27(10):1283-1294. doi: 10.1007/s00787-018-1113-4. Epub 2018 Feb 13.