Maintenance of Efficacy of Extended-Release Guanfacine HCl in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD)

Official Title: “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”

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.

Intervention(s) in this Clinical Trial

• Drug: Extended-release Guanfacine Hydrochloride
  • The test product will be provided as 1, 2, 3, and 4mg tablets. Subjects will be administered a once-daily dose between 1-7mg/day depending on age and weight.
• Other: Placebo
  • Matching placebo will be provided as 1, 2, 3, and 4mg tablets. Subjects will be administered a once-daily dose of placebo between 1-7mg/day depending on age and weight.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Extended-release Guanfacine HCl
• Placebo Comparator: Placebo

Primary Measures

• Attention deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV)
  • Time Frame: weekly
    Safety Issue?: No
• Clinical Global Impressions- Severity of Illness Scale (CGI-S)
  • Time Frame: weekly
    Safety Issue?: No

Secondary Measures

• Clinical Global Impressions-Improvement Scale (CGI-I)
  • Time Frame: weekly
    Safety Issue?: No
• Weiss Functional Impairment Rating Scale-Parent (WFIRS-P)
  • Time Frame: weekly
    Safety Issue?: No
• Health Utilities Index-Mark 2 and Mark 3 (HUI-2/3)
  • Time Frame: weekly
    Safety Issue?: No
• Columbia-Suicide Severity Rating Scale (C-SSRS)
  • Time Frame: weekly
    Safety Issue?: Yes

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)
• Guideline E6 (1996) and applicable regulations before completing any study-related procedures at Screening/Visit 1.
• 3. 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).
• 4. Subject has a minimum ADHD-RS-IV total score of 32 at Enrolment/Visit 2.
• 5. Subject has a minimum CGI-S score of 4 at Enrolment/Visit 2.
• 6. Subject is functioning at an age-appropriate level intellectually, as deemed by the Investigator.
• 7. Subject and parent/LAR understand, are willing, able, and likely to fully comply with the study requirements, procedures, and restrictions defined in this protocol.
• 8. Subject is able to swallow intact tablets.
• 9. 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.
• 10. Subject has a supine and standing BP measurement within the 95th percentile for age, gender, and height.

Exclusion Criteria:

• 1. 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.
• 2. 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.
• 3. 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.
• 4. Subject with orthostatic hypotension or a known history of controlled or uncontrolled hypertension.
• 5. Subject has clinically significant ECG findings as judged by the Investigator with consideration of the central ECG laboratory's interpretation.
• 6. 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 2.
• 7. Subject has used an investigational product within 30 days prior to Enrolment/Visit 2.
• 8. 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.
• 9. 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 1.
• 10. Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride or any components found in SPD503.
• 11. Clinically important abnormality on drug and alcohol screen (excluding the subject's current ADHD stimulant if applicable) at Screening/Visit 1.
• 12. Subject has a history of alcohol or other substance abuse or dependence, as defined by DSM-IV-TR (with the exception of nicotine) within the last 6 months.
• 13. Subject is female and is pregnant or currently lactating.
• 14. Subject failed screening or was previously enrolled in this study.
• 15. 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 (see protocol Section 7.2.4.2 for additional guidance).
• 16. History of failure to respond to an adequate trial of an alpha 2-agonist for the treatment of ADHD (consisting of an appropriate dose and adequate duration of therapy in the opinion of the Investigator).
• 17. 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).
• 18. Subject has another member of the same household currently participating in this study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Years

Maximum Age for this Clinical Trial: 17 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Shire Pharmaceutical Development Industry

Overall Clinical Trial Officials and Contacts

Jeffrey H. Newcorn, M.D. Principal Investigator Mount Sinai School of Medicine  

Overall Contact: Shire Call Center +1 866-842-5335 

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01081145

Study ID Number: SPD503-315

ClinicalTrials.gov Identifier: NCT01081145

Health Authority: United States: Food and Drug Administration