Maintenance of Efficacy of Extended-Release Guanfacine HCl in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD)
Condition: Attention-deficit/Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: Extended-release Guanfacine Hydrochloride; Placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Guanfacine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 528.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.