Dose-optimization in Adolescents Aged 13-17 Diagnosed With Attention-deficit/Hyperactivity Disorder (ADHD) Using Extended-release Guanfacine HCl
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 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 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: 314.0
Sex: All
Minimum age: 13 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      To assess the efficacy of optimized Extended-release Guanfacine Hydrochloride compared with
      placebo in the treatment of adolescents aged 13-17 years with a diagnosis of ADHD as measured
      by the ADHD-RS-IV
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, aged 13-17 years at the time of consent/assent (screening only).

          2. Subject's parent or legally authorized representative (LAR) must provide signature of
             informed consent, and there must be documentation of assent 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 (1996) and applicable
             regulations before completing any study-related procedures at screening.

          3. Subject meets Diagnostic and Statistical Manual of Mental Disorders, Fourth
             Edition-Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD, combined
             subtype, or hyperactive/impulsive subtype, based on a detailed psychiatric evaluation
             using the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and
             Lifetime version (K SADS PL) at screening (re-confirm if baseline visit is >35 days
             from screening).

          4. Subject has a minimum ADHD-RS-IV total score of 32 at baseline.

          5. Subject has a minimum CGI-S score of 4 at baseline.

          6. Subject is functioning at an age-appropriate level intellectually, as deemed by the
             Investigator.

          7. Subject and parent/LAR understand, are able, willing and likely to fully comply with
             the study procedures and restrictions defined in this protocol.

          8. Subject is able to swallow intact tablets.

          9. All females must have a negative serum beta human Chorionic Gonadotropin (hCG)
             pregnancy test at screening and a negative urine pregnancy test at baseline. Female
             subjects must abstain from sexual activity that could result in pregnancy or agree to
             use acceptable methods of contraception.

         10. Subject has a supine and standing blood pressure (BP) measurement within the 95th
             percentile for age, gender, and height.

        Exclusion Criteria:

          1. Subject has a current, controlled (requiring a prohibited medication or behavioral
             modification program) or uncontrolled, comorbid psychiatric diagnosis [except
             Oppositional Defiant Disorder (ODD), but including all anxiety disorders (except
             simple phobias)], all major depressive disorders (dysthymia allowed unless medication
             required), and 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 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 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 has any abnormal or clinically significant ECG findings as judged by the
             Investigator with consideration of the central ECG interpretation.

          5. Subject with orthostatic hypotension or a known history of controlled or uncontrolled
             hypertension.

          6. Current use of any prohibited medication, including herbal supplements that affect
             blood pressure, heart rate, 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 (i.e., antihistamines) at baseline.

          7. Subject has a history of alcohol or other substance abuse or dependence, as defined by
             DSM IV-TR (with the exceptions of nicotine) within the last six months.

          8. Subject has taken another investigational product within 30 days prior to baseline.

          9. Subject is significantly overweight based on Center for Disease Control and Prevention
             Body Mass Index (BMI)-for-age gender specific charts at screening. Significantly
             overweight is defined as a BMI >95th percentile for this study.

         10. Body weight of less than 34.0kg or greater than 91.0kg at screening.

         11. Subject has a known or suspected allergy, hypersensitivity, or clinically significant
             intolerance to guanfacine hydrochloride or any components found in SPD503.

         12. Clinically important abnormality on urine drug and/or alcohol screen (excluding the
             subject's current ADHD stimulant if applicable).

         13. Subject is female and is pregnant or currently lactating.

         14. Subject failed screening or was previously enrolled in this study.

         15. Subject who is currently considered a suicide risk, has previously made a suicide
             attempt, or has a prior history of, or is currently demonstrating suicidal ideation.

         16. History of failure to respond to an adequate trial (consisting of an appropriate dose
             and adequate duration of therapy), in the opinion of the Investigator, of an
             α2-agonist for the treatment of ADHD.

         17. Subject has a history of a seizure disorder (other than a single childhood febrile
             seizure occurring before the age of 3 years) or a history of a tic disorder (including
             Tourette's syndrome).