A Phase 3, Double-blind, Placebo-controlled, Multicentre, Randomised Withdrawal, Long-term Maintenance of Efficacy and Safety Study of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 With Attention Deficit/Hyperactivity Disorder

Shire79 sites in 5 countries528 target enrollmentMay 11, 2010

ConditionsAttention-deficit/Hyperactivity Disorder

InterventionsExtended-release Guanfacine Hydrochloride Placebo

DrugsExtended-release Guanfacine Hydrochloride

Overview

Phase: Phase 3
Intervention: Extended-release Guanfacine Hydrochloride
Conditions: Attention-deficit/Hyperactivity Disorder
Sponsor: Shire
Enrollment: 528
Locations: 79
Primary Endpoint: Percentage of Participants With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objective of this study is to evaluate the long-term maintenance of efficacy of Extended-Release Guanfacine HCl in children and adolescents (6-17 years) with attention-deficit/hyperactivity disorder (ADHD) who respond to an initial open-label, short term treatment with SPD503.

Registry

clinicaltrials.gov

Start Date

May 11, 2010

End Date

June 3, 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
•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 (1996) and applicable regulations before completing any study-related procedures at Screening/Visit
•Subject meets DSM-IV-TR criteria for a primary diagnosis of ADHD, combined subtype, hyperactive/impulsive subtype, 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 Enrolment/Visit
•Subject has a minimum CGI-S score of 4 at Enrolment/Visit
•Subject is functioning at an age-appropriate level intellectually, as deemed by the Investigator.
•Subject and parent/LAR understand, are willing, able, and likely to fully comply with the study requirements, procedures, and restrictions defined in this protocol.
•Subject is able to swallow intact tablets.
•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 Screening/Visit 1 and a negative urine pregnancy test at Enrolment/Visit 2 and agree to comply with any applicable contraceptive requirements of the protocol.
•Subject has a supine and standing BP measurement within the 95th percentile for age, gender, and height.

Exclusion Criteria

•Subject has a current, controlled (requiring a prohibited medication or behavioural modification program) or uncontrolled, comorbid psychiatric diagnosis, except oppositional defiant disorder (ODD), 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 SPD503 treatment or confound efficacy or safety assessments.
•Subject has any condition or illness including 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.
•Subject has a known history or presence of structural cardiac abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction problems (e.g., 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.
•Subject has clinically significant ECG findings as judged by the Investigator with consideration of the central ECG laboratory's interpretation.
•Current use of any prohibited medication or other medications, including herbal supplements, that affect BP or heart rate or that have 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 \[i.e., antihistamines\]) in violation of the protocol specified washout criteria at Enrolment/Visit
•Subject has used an investigational product within 30 days prior to Enrolment/Visit
•Subject is significantly overweight based on Centre for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts. Significantly overweight is defined as a BMI \>95th percentile.
•Children aged 6-12 years with a body weight of \<25kg or adolescents aged 13-17 years with a body weight of \<34kg or \>91kg at Screening/Visit
•Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride or any components found in SPD

Arms & Interventions

Extended-release Guanfacine HCl

Intervention: Extended-release Guanfacine Hydrochloride

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Percentage of Participants With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase

Time Frame: 26 weeks

Treatment failure was defined as \>= 50% increase (worsening) in ADHD-RS-IV total score and a \>= 2 point increase (worsening) in CGI-S score compared with the respective scores at the Double-blind Randomized-withdrawal Baseline Visit at 2 consecutive Double-blind Randomized-withdrawal Phase visits. Subjects meeting these criteria were regarded as treatment failures regardless of whether or not they were withdrawn. All subjects who discontinued the study for any reason were regarded as treatment failures for the primary analysis.

Secondary Outcomes

Change From Double-Blind Randomized-Withdrawal Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - Last Observation Carried Forward (LOCF)(Baseline and week 26)
Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale During the Double-Blind Randomized-Withdrawal Phase - LOCF(26 weeks)
Columbia-Suicide Severity Rating Scale During Double-Blind Randomized-Withdrawal Phase(26 weeks)
Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores During Open-Label Phase - LOCF(13 weeks)
Time to Treatment Failure During the Double-Blind Randomized-Withdrawal Phase(26 weeks)
Health Utilities Index-2/3 (HUI 2/3) Scores During the Double-Blind Randomized-Withdrawal Phase - LOCF(26 weeks)
Change From Open-Label Baseline in ADHD-RS-IV Total Score at Week 13 of the Open-Label Phase - LOCF(Baseline and 13 weeks)
Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on CGI-S Scale During the Open-Label Phase - LOCF(13 weeks)
Change From Open-Label Baseline in WFIRS-P Global Score at Week 13 of the Open-Label Phase - LOCF(Baseline and week 13)
HUI 2/3 Scores During the Open-Label Phase - LOCF(13 weeks)
Columbia-Suicide Severity Rating Scale During Open-Label Phase(13 weeks)
Change From Double-Blind Randomized-Withdrawal Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - LOCF(Baseline and week 26)
Percentage of Responders in the Open-Label Phase - LOCF(13 weeks)