Dose-optimization in Adolescents Aged 13-17 Diagnosed With Attention-deficit/Hyperactivity Disorder (ADHD) Using Extended-release Guanfacine HCl

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).