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

Shire66 sites in 10 countries338 target enrollmentJanuary 17, 2011

ConditionsAttention Deficit Hyperactivity Disorder

InterventionsExtended-release Guanfacine Hydrochloride Atomoxetine Hydrochloride Placebo Comparator

DrugsExtended-release Guanfacine Hydrochloride Atomoxetine Hydrochloride Placebo Comparator

Overview

Phase: Phase 3
Intervention: Extended-release Guanfacine Hydrochloride
Conditions: Attention Deficit Hyperactivity Disorder
Sponsor: Shire
Enrollment: 338
Locations: 66
Primary Endpoint: 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)
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

Registry

clinicaltrials.gov

Start Date

January 17, 2011

End Date

May 1, 2013

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Shire

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.
•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

Exclusion Criteria

•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.
•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).

Arms & Interventions

Extended-release Guanfacine Hydrochloride

Intervention: Extended-release Guanfacine Hydrochloride

Atomoxetine Hydrochloride

Active Reference

Intervention: Atomoxetine Hydrochloride

Placebo

Intervention: Placebo Comparator

Outcomes

Primary Outcomes

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.

Secondary Outcomes

Clinical Global Impression-Severity of Illness (CGI-S) - LOCF(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(Baseline and 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(Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years)
Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores(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(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(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(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(Baseline and up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years)
Columbia-Suicide Severity Rating Scale (C-SSRS)(Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years)
Change From Baseline in the WFIRS-P Behavior in School Domain Score at Week 10/13 - LOCF(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(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(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 Social Domain Score at Week 10/13 - LOCF(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(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(Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years)