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

This study has been completed.
Sponsor:
Information provided by:
Shionogi Inc.
ClinicalTrials.gov Identifier:
NCT01439126
First received: September 13, 2011
Last updated: May 21, 2013
Last verified: May 2013
  Purpose

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)


Condition Intervention Phase
Attention Deficit Hyperactivity Disorder
Drug: KAPVAY™ (clonidine hydrochloride)
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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 Attention Deficit Hyperactivity Disorder

Resource links provided by NLM:


Further study details as provided by Shionogi Inc.:

Primary Outcome Measures:
  • Long-term maintenance of efficacy of KAPVAY™ in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) as measured by the percentage of treatment failures in the KAPVAY™ vs. placebo groups [ Time Frame: From randomization to end of the randomized-withdrawal period (26 weeks) ] [ Designated as safety issue: No ]
    Treatment failure is defined as a ≥30 percentage increase (worsening) in Attention Deficit Hyperactivity Disorder-Rating Scale-4th edition (clinician version) total score and a ≥2 point increase (worsening) in Clinical Global Impressions-Severity of Illness Scale at any two consecutive visits during Period 3 relative to Visit 9 (randomization visit)


Secondary Outcome Measures:
  • To evaluate the long-term efficacy of Kapvay™ in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) as measured by the time to treatment failure from the start of randomized-withdrawal period [ Time Frame: From randomization to treatment failure ] [ Designated as safety issue: No ]
    Time to treatment failure was calculated as follows: Treatment failure (not premature termination) = visit date where the failure criteria was met - visit 9 date + 1; Treatment failure (premature termination) = termination date - visit 9 date + 1

  • Long-term efficacy of KAPVAY™ in children and adolescents with ADHD as measured by the change from randomization to the end of the randomized-withdrawal period on the ADHD-Rating Scale-4th edition (ADHD-RS-IV) [ Time Frame: From randomization to end of the randomized-withdrawal period (26 weeks) ] [ Designated as safety issue: No ]
    The ADHD-RS-IV (clinician version), has been widely used as a measure of efficacy in clinical trials of treatments in children and adolescents with ADHD. It is derived from the 18 inattentive and hyperactive/impulsive diagnostic criteria for ADHD from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). The clinician version of the ADHD-RS-IV has a large base of normative data and has demonstrated reliability and discriminant validity in children and adolescents

  • Long-term efficacy of KAPVAY™ in children and adolescents with ADHD as measured by the change from randomization to the end of the randomized-withdrawal period on the Clinical Global Impressions-Severity of Illness Scale (CGI-S) [ Time Frame: From randomization to end of the randomized-withdrawal period (26 weeks) ] [ Designated as safety issue: No ]
    The CGI-S is a clinician rated instrument designed to assess the subject's current illness state. The CGI-S consists of 7 ratings that range from 1 = "Normal, not at all ill" to 7 = "Among the most extremely ill subjects"

  • Long-term efficacy of KAPVAY™ in children and adolescents with ADHD as measured by the change from randomization to the end of the randomized-withdrawal period on the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P) [ Time Frame: From randomization to end of the randomized-withdrawal period (26 weeks) ] [ Designated as safety issue: No ]
    The WFIRS-P is designed to assess the impact of child's behavior or emotional problems on 5 domains of functioning: family; learning at school; life skills; self concept; social activities; and risky activities. The scale has 50 questions, each scored on a 4-point scale ranging from 0 (Never or Not at all) to 3 (Very often or Very much)

  • Long-term efficacy of KAPVAY™ in children and adolescents with ADHD as measured by the change from randomization to the end of the randomized-withdrawal period on the Epworth Sleepiness Scale for Children (ESS-C) [ Time Frame: From randomization to end of the randomized-withdrawal period (26 weeks) ] [ Designated as safety issue: No ]
    The ESS-C is a simple eight-item Likert scale designed to assess daytime sleepiness in children aged 2-18 years in variety of settings. The scale takes less than two minutes to be completed by patient or by parent rating. Sleepiness is a common symptom in both medicated and unmedicated children with ADHD given the predominance of impaired sleep quality. The total score achieved when the chance of dozing in each situation is added up serves as the outcome measure. This scale is modified version of the ESS deleting reference to alcohol and adding references to settings such as the classroom

  • Long-term safety of of KAPVAY™ in children and adolescents with ADHD [ Time Frame: From study start to study end (40 weeks) ] [ Designated as safety issue: Yes ]
    Assessment of adverse events, serious adverse events, adverse events leading to study drug discontinuation, clinical laboratory evaluations, vital signs, electrocardiograms, and any changes in the Columbia Suicide Severity Rating Scale


Enrollment: 135
Study Start Date: August 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Subjects on KAPVAY™ (clonidine hydrochloride)
Subjects in the KAPVAY™ arm continued to receive their optimal dose of KAPVAY™ (ie, Period 2 Maintenance Dose) for the duration of the 26-week randomized-withdrawal period (Period 3)
Drug: KAPVAY™ (clonidine hydrochloride)
KAPVAY™ (clonidine hydrochloride) 0.1 mg, 0.2 mg, 0.3 mg, or 0.4 mg from Weeks 11-36
Subjects on Placebo
Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY™ (ie, Period 2 Maintenance Dose) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day; subjects then continued to receive only placebo for the rest of the study
Drug: Placebo
KAPVAY™ (clonidine hydrochloride) 0.1 mg, 0.2 mg, or 0.3 mg at Week 11; KAPVAY™ 0.1 mg, KAPVAY™ 0.2 mg, or placebo at Week 12; KAPVAY™ 0.1 mg or placebo at Week 13; placebo from Weeks 14-36

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, aged 6 to 17 years inclusive, at the time of assent/consent at screening (Visit 1)
  • 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, able, and likely 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. These conditions include any severe comorbid axis II disorders or severe axis I disorders such as bipolar illness, psychosis, pervasive developmental disorder, post traumatic stress 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 KAPVAY™ treatment or confound efficacy or safety assessments
  • 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. Pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test (> 5 mIU/mL)
  • 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. Specifically, a QTc-Fridericia repeatedly > 450 milliseconds in males or > 470 milliseconds in females at screening visit will be exclusionary
  • 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. Significantly underweight is defined as a BMI of <5th percentile
  • 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. Subjects who fail routine urine screening for substances of abuse can be rescreened once and permitted into the trial following consultation with the medical monitor who must make an assessment that the subject is not at risk of abuse during the study period
  • 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). Specifically any positive response on C-SSRS items 4 or 5 at screening are exclusionary
  • 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. An adequate trial assumes that patients were ostensibly compliant with an appropriate dose and adequate duration of therapy in the opinion of the investigator
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01439126

Sponsors and Collaborators
Shionogi
Investigators
Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line Shionogi
  More Information

No publications provided

Responsible Party: Shionogi Clinical Trials Administrator, Shionogi
ClinicalTrials.gov Identifier: NCT01439126     History of Changes
Other Study ID Numbers: SHN-KAP-401
Study First Received: September 13, 2011
Last Updated: May 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Shionogi Inc.:
Attention Deficit Hyperactivity Disorder

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Clonidine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014