Access to Extended Release Guanfacine HCl for Subjects Who Participated in Studies SPD503-315 or SPD503-316 in Europe

NCT01500694 | Completed Phase 3 Results DMC

• 2 other identifiers: SPD503-3182011-004668-31
• Study Type: interventional
• Target: 215
• Locations: 13 countries
• Sites: 60

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).

Conditions

Attention Deficit Hyperactivity Disorder (ADHD)

Outcome Measures

Primary Outcomes (8)

• Change From Baseline in Mean Systolic Blood Pressure at Final Assessment

  Systolic Blood pressure was measured at supine and standing position and mean supine systolic blood pressure was reported here. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication \[Visit 19/Early Termination (ET)/Day 714\].

  Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

• Change From Baseline in Mean Diastolic Blood Pressure at Final Assessment

  Diastolic Blood pressure was measured at supine and standing position and mean supine diastolic blood pressure was reported here. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

  Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

• Change From Baseline in Mean Supine Pulse at Final Assessment

  Pulse was measured at supine and standing position and mean supine pulse was reported here. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

  Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

• Change From Baseline in Mean Height at Final Assessment

  Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

  Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

• Change From Baseline in Mean Weight at Final Assessment

  Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

  Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

• Change From Baseline in Electrocardiogram Result (QRS Interval) at Final Assessment

  Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

  Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

• Change From Baseline in Electrocardiogram Result (QT Interval) at Final Assessment

  Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

  Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

• Number of Participants With Suicidal Behavior and / or Ideation ("Yes" Response) on the Columbia Suicide Severity Rating Scale (C-SSRS)

  C-SSRS is a clinician rated assessment of suicidal behavior and / or intent categorized as: Suicidal behavior=a "yes" response to any of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide); Suicidal ideation=a "yes" response to any one of 5 suicidal ideation questions which includes wish to be dead, and 4 different categories of active suicidal ideation (thought, thought with method, thought with intent, thought with plan and intent).

  Final Assessment (last non missing data/up to Day 714)

Secondary Outcomes (2)

• Change From Baseline in Attention-deficit and Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) - Total Score at Final Assessment

  Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

• Number of Participants Assessed With Clinical Global Impression Severity of Illness (CGI-S) Scale

  Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Study Arms (1)

Extended-release Guanfacine HCl

EXPERIMENTAL

Drug: Extended-release Guanfacine HCl (Intuniv, SPD503)

Interventions

Extended-release Guanfacine HCl (Intuniv, SPD503) DRUG

Subjects will be dosed orally once-daily in the AM at 1, 2, 3, 4, 5, 6, or 7 mg according to subjects weight and age

Also known as: Intuniv, SPD503

Extended-release Guanfacine HCl

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Subject satisfied all entry criteria for the antecedent study (SPD503 315 or SPD503-316).
• 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.
• 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.
• 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.
• Subject has a supine and standing blood pressure (BP) measurement within the 95th percentile for age, sex, and height.
• Subject is functioning at an age-appropriate level intellectually, as deemed by the Investigator.
• Subject is able to swallow intact tablets.

You may not qualify if:

• 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.
• 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.
• 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.
• Clinically important abnormality on urine drug and/or alcohol screen at the Screening Visit (Visit 1).
• 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).
• 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.
• 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).
• 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.
• 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.
• 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).
• Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride, or any components found in SPD503.
• 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.
• 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 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.
• Subject with orthostatic hypotension or a known history of controlled or uncontrolled hypertension.

Sponsors & Collaborators

• Shire: lead

Study Sites (60)

Medizinische Universitat Graz Univ fur Kinder

Graz, 6036, Austria

Location

Institut fur Psychosomatik

Vienna, 1010, Austria

Location

Universitaire Kinder-end Jeugdpsychatrie

Hoboken, 2660, Belgium

Location

Centre de Reference Neuropediatrique Multidisciplinaire

Namur, 5000, Belgium

Location

Huisartspraktijk Jaak Mortelmans

Oostham, 3845, Belgium

Location

Zlekenhuis Inkendaal Koninklijke Instelling v.z.w.

Vlezenbeek, 1602, Belgium

Location

Centre Hospitalier Universitaire Amiens

Amiens, Picardie, 80054, France

Location

Centre Hospitalier Charles Perrens

Bordeaux, 33076, France

Location

Hopital Gui de Chauliac

Montpellier, 34295, France

Location

Dr. med. Andreas Mahler

Achim, 28632, Germany

Location

Emovis GmbH

Berlin, 10629, Germany

Location

Sozialpsychitrisches Zentrum

Dorsten, 46282, Germany

Location

Klinik und Poliklinik fur Kinder-und Jugendpsychiatrie un psychotherapie

Dresden, 01307, Germany

Location

Dr. med Walter Robert Otto

Fulda, 36037, Germany

Location

Dr. med. Christian Wolff

Hagen, 58093, Germany

Location

Dr. med Friedrich Kaiser

Hamburg, 22415, Germany

Location

Institut fur Ganzheitliche Medizin und Wissenschaft GmbH

Hüttenberg, 35625, Germany

Location

Friedrich Schiller Universitat Jena Klinik fur Kinder und Jugendpsychiatrie

Jena, 07743, Germany

Location

Universitatsmedizin der Johannes-Gutenberg-Universitat

Mainz, 55131, Germany

Location

Kinder-und Jugendpsychiatrische Praxis

München, 81241, Germany

Location

Somni bene GmbH Institut fur Medizinische Forschung und Schlatmedizin

Schwerin, 19053, Germany

Location

Universitatsklinik Ulm

Ulm, 89075, Germany

Location

Our Lady's Children's Hospital

Crumlin, Dublin, 12, Ireland

Location

Azienda Ospedaliero-Universitaria Policlinico-Vittorio

Catania, 95123, Italy

Location

Azienda Ospedallera G Salvini - Ospedale Di Circolo de RHO

Milan, 20017, Italy

Location

Azienda Ospedallera Fatebenefratelli

Milan, 20129, Italy

Location

U.O di Neuropsichiatria Infantile

Padua, 35143, Italy

Location

IRCCS Fondazione Stella Maris

Pisa, 56018, Italy

Location

Ospedale Policlinico GB Rossi

Verona, 37134, Italy

Location

Flevo Research

Almere Stad, 1311 RL, Netherlands

Location

Mondriaan Zorggroep

Heerlen, 6419 XZ, Netherlands

Location

NZOZ Gdanskie Centrum Zdrowia

Gdansk, 80-542, Poland

Location

Centrum Badari Klinicznych House Sp. z.o.o.

Gdansk, 80-546, Poland

Location

Gabinet Psychiatrii Doroslych, Dzieci i Mlodziezy

Torun, 87-100, Poland

Location

Indywidualna Specjalisyczna Praktyka Lekarska

Torun, 87-100, Poland

Location

Contrum Neurospychiatrii Neuromed

Wroclaw, 54-2353, Poland

Location

Spitalul Clinic de Urgenta pentru Copli

Timișoara, Timiș County, 300239, Romania

Location

Spitalul Clinic de Psihiatrie

Bucharest, 041914, Romania

Location

Spitalul Clinic de Psihiatrie Socoia

Iași, 700282, Romania

Location

Hospital Mutua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Hospital Universitani Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Infanta Leonor, Servicio de Psiquiatria

Madrid, 28031, Spain

Location

Hospital Fundacion Alcorcon

Madrid, 28922, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, 07198, Spain

Location

Unidad de Salud Mental Infanto Juvenil

Santander, 39011, Spain

Location

Instituto Valenciano de Neurologia Pediatrica

Valencia, 46010, Spain

Location

Drottning Silvias Barnsjukhus

Gothenburg, SE-411 18, Sweden

Location

Regional Clinical Psychiatric Hospital

Donetsk, 83008, Ukraine

Location

Institute of Neurology, Psychiatry and Narcology

Kharkiv, 61068, Ukraine

Location

Institute of Health Care for Children and Teenagers

Kharkiv, Ukraine

Location

Lviv Regional Clinical Psychiatric Hospital

Lviv, 79021, Ukraine

Location

Odesa Regional Psychoneurological Dispensary

Odesa, 65084, Ukraine

Location

Poltava Regional Clinical Psychiatric Hospital

Poltava, 36013, Ukraine

Location

Vinnitsya regional psychoneurological hospital

Vinnytsia, 21005, Ukraine

Location

Lister Hospital

Stevenage, Herfordshire, United Kingdom

Location

Queen Elizabeth II Hospital - Howlands

Welwyn Garden City, Herfordshire, AL7 4HQ, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

West Derby, Liverpool, L12 2AP, United Kingdom

Location

The Children's Centre

Norwich, NR4 7PA, United Kingdom

Location

Ryegate Children's Centre

Sheffield, S10 5DD, United Kingdom

Location

Centenary House Child and Adolescent Mental Health Services

Sheffield, S6 3BR, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29442229 RESULT

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Guanfacine

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2011
• First Posted: December 28, 2011
• Study Start: March 20, 2012
• Primary Completion: September 15, 2015
• Study Completion: September 15, 2015
• Last Updated: June 16, 2021
• Results First Posted: May 18, 2017

Record last verified: 2021-05

Locations

AU (2); FR (3); PL (5); ES (7); IE (1); NL (2); BE (4); RO (3); SE (1); DE (13); IT (6); UA (7); GB (6)