Efficacy & Safety of KAPVAY™ Extended-Release in Children & Adolescents With Attention Deficit Hyperactivity Disorder

A 40-Week, Phase 4, Double-Blind, Placebo-Controlled, Multicenter, Randomized-Withdrawal Study to Evaluate the Long-Term Efficacy and Safety of KAPVAY™ (Clonidine Hydrochloride) Extended-Release in Children and Adolescents With ADHD

The purpose of this study is to determine the long-term efficacy and safety of KAPVAY™ (clonidine hydrochloride) extended-release in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD)

Inclusion Criteria:

• Male or female, aged 6 to 17 years inclusive
• Subject as well as parent/guardian is able to sign the informed assent or consent form
• Subject meets Diagnostic and Statistical Manual of Mental Disorders 4th edition, Text Revision (DSM-IV-TR) criteria for a primary diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), combined subtype, hyperactive/impulsive subtype, or inattentive sub-type based on a detailed psychiatric evaluation using the Shorter version of the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (MINI-Kid) or DSM-IV TR based checklist for ADHD
• Subject has a minimum of Attention Deficit Hyperactivity Disorder-Rating Scale-4th edition (clinician version) total score of 28 at baseline (Visit 2)
• Subject has a minimum of Clinical Global Impressions-Severity of Illness Scale of 4 at baseline (Visit 2)
• Subject is able to swallow intact tablets based upon interview and screening procedures
• Subject is functioning at an age-appropriate level intellectually with an estimated intelligence quotient of at least 70 based on interview and history
• Subject and parent/guardian understand, are willing, to fully comply with the study requirements, procedures, and restrictions defined in this protocol
• Subject has a supine and standing blood pressure measurement within the 95th percentile for age, gender, and height
• If a female has experienced menarche, she must have a negative serum beta human chorionic gonadotropin pregnancy test at screening (Visit 1), negative urine pregnancy test at baseline (Visit 2), agree to be abstinent from sexual activity that could result in pregnancy, or use acceptable contraceptives throughout the period of the study drug exposure and for 30 days after the last dose of the study drug

Exclusion Criteria:

• Subject has a current comorbid psychiatric condition (except oppositional defiant disorder) that is controlled (requiring a prohibited medication or behavioral modification program) or uncontrolled.
• Subject has any condition or illness including clinically significant abnormal screening (Visit 1) laboratory values that, 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 (eg, clinically significant heart block), exercise-related cardiac events including syncope and presyncope, or clinically significant bradycardia
• Subject is pregnant or nursing (lactating) or deemed by the investigator and staff to be at a significant risk of becoming pregnant.
• Subject has orthostatic hypotension or a known history of controlled or uncontrolled hypertension
• Subject has clinically significant electrocardiogram (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 blood pressure, or heart rate, or that have central nervous system 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 (ie, antihistamines) in violation of the protocol specified washout criteria at baseline (Visit 2)
• Subject has used an investigational product within 30 days prior to baseline (Visit 2)
• Subject is significantly overweight based on body mass Index (BMI) for age-and gender-specific charts compiled by Center for Disease Control and Prevention. Significantly overweight is defined as a BMI of ≥95th percentile
• Subject is significantly underweight based on BMI for age-and gender-specific charts compiled by Center for Disease Control and Prevention.
• Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to clonidine hydrochloride
• Clinically important abnormality on drug and alcohol screening (excluding the subject's current ADHD stimulant if applicable) at screening (Visit 1)
• Subject has a history of alcohol, other substance abuse, or dependence as defined by DSM-IV-TR (with the exception of nicotine) within the last 6 months.
• Subject is currently considered a suicidal risk in the opinion of the investigator, has previously made a suicide attempt, has a prior history of, or is currently demonstrating active suicidal ideation based on the Columbia Suicide Severity Rating Scale (C-SSRS).
• Subject has a history of failure to respond to an adequate trial of an alpha 2-agonist with stimulant or non-stimulant drug alone or in combination for the treatment of ADHD.
• 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 syndrome)
• Subjects who have been treated with an immediate release clonidine and/ KAPVAY™ or guanfacine (INTUNIV™) within the past 30 days