Open-Label, Chronic Exposure, Safety Study of CLONICEL (Clonidine HCl Sustained Release) in Children and Adolescents With Attention Deficit Hyperactivity Disorder (ADHD)

An Open-Label, Chronic Exposure Evaluation of the Safety of CLONICEL (Clonidine HCl Sustained Release) in the Treatment of Children and Adolescents With Attention Deficit Hyperactivity Disorder (ADHD)

The purpose of this 12-month, multi-center, open-label study is to evaluate the safety of CLONICEL (clonidine HCl sustained release) when administered chronically under regular clinical conditions either as monotherapy or in combination with stimulant therapy to children and adolescents with attention deficit hyperactivity disorder (ADHD).

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: CLONICEL (Clonidine HCl sustained release)

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • El Centro, California, United States, 92243
    • Irvine, California, United States, 92612
    • San Diego, California, United States, 92103
  • Florida
    • Bradenton, Florida, United States, 34208
    • Gainesville, Florida, United States, 32607
    • Jacksonville, Florida, United States, 32216
    • Lauderhill, Florida, United States, 33319
    • Miami, Florida, United States, 33161
    • Orlando, Florida, United States, 32806
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
  • Maryland
    • Baltimore, Maryland, United States, 21208
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
  • Missouri
    • Saint Louis, Missouri, United States, 63005
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
    • Willingboro, New Jersey, United States, 08046
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
    • Charlotte, North Carolina, United States, 28209
    • Durham, North Carolina, United States, 27705
  • Ohio
    • Cleveland, Ohio, United States, 44106
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
    • Oklahoma City, Oklahoma, United States, 73116
  • Texas
    • Houston, Texas, United States, 77007
    • Lake Jackson, Texas, United States, 77566
    • Wharton, Texas, United States, 77488
  • Utah
    • Clinton, Utah, United States, 84015
  • Washington
    • Kirkland, Washington, United States, 98033

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subject who has completed either study CLON-301 or study CLON-302, or discontinued early for reasons other than adverse events necessitating discontinuation
• Age between 6 and 17 years, inclusive
• Diagnosis of attention deficit hyperactivity disorder of the hyperactive or combined inattentive/hyperactive subtypes according to Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) criteria
• General good health as judged by the Principal Investigator
• Body mass index (BMI) ≥ 5th percentile of the subject's age group according to the CDC growth chart. BMI is calculated using the formula: weight (kg) / [height (m)]2
• Subject as well as parent/guardian able to sign informed assent or consent form

Exclusion Criteria:

• If female of child-bearing potential, pregnant or lactating or does not agree to use a medically acceptable form of birth control, such as hormonal medication, double-barrier method, or intrauterine device
• Presence of a clinically significant illness or abnormality on physical examination or clinical laboratory evaluations that, in the opinion of the investigator, would increase the safety risks from clonidine administration or interfere with the ability of the patient to take part in the study.
• Presence of clinically significant abnormality on centrally interpreted electrocardiogram readings
• History or presence of a concomitant psychiatric disorder requiring psychotropic medication or a severe concomitant axis I or axis II disorder that could interfere with study assessments in the judgment of the Principal Investigator
• Presence of a disorder that would interfere with the absorption, metabolism, or excretion of clonidine
• Presence of alcohol or drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; CLONICEL (Clonidine HCl sustained release)	Drug: CLONICEL (Clonidine HCl sustained release); 0.1 mg for 1 week; the dose may be escalated to 0.2 mg/day at week 2, 0.3 mg/day at week 3, and 0.4 mg/day at week 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessment in Terms of Adverse Events (Treatment-emergent [TEAEs] and Serious [SAEs])	Safety assessments were performed at each study visit according to the time and events schedule. All safety analyses were based on safety population	1 year
Safety Assessment in Terms of Adverse Events (Treatment-emergent [TEAEs] and Serious [SAEs])	Safety assessments were performed at each study visit according to the time and events schedule. All safety analysis were based on safety population	1 year
Change From Baseline in 12-lead Electrocardiogram in Terms of QT, QTc Fridericia (QTcF), and QTc Bazett's (QTcB) at Week 4		At baseline and at Week 4
Change From Baseline in Body Weight at Weeks 1, 2, 3, 4, and Months 2, 3, 4, 5, 6, 9, and 12		At baseline and at weeks 1, 2, 3, 4, and months 2, 3, 4, 5, 6, 9, and 12
Change From Baseline in Diastolic Blood Pressure at Week 4	Blood pressure was measured with the subject in a sitting position and resting for at least 2 minutes prior to taking the measurement. The dominant arm was used for the measurement	At baseline and at Week 4
Change From Baseline in Systolic Blood Pressure at Week 4	Blood pressure was measured with the subject in a sitting position and resting for at least 2 minutes prior to taking the measurement. The dominant arm was used for the measurement	At baseline and at Week 4
Change From Baseline in Body Temperature at Week 4	Temperature was measured with the subject in a sitting position and resting for at least 2 minutes prior to taking the measurement	At baseline and at Week 4
Change From Baseline in Heart Rate at Week 4	Heart rate was measured with the subject in a sitting position and resting for at least 2 minutes prior to taking the measurement	At baseline and at Week 4
Change From Baseline in 12-lead Electrocardiogram in Terms of Heart Rate at Week 4		At baseline and at Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHDRS-IV Scale) (18 Items Scored, 0 [Never/Rarely] to 3 [Very Often]; Total Possible Score Range, 0-54) at Months 1, 2, 3, 4, 6, 9, and 12	The ADHDRS-IV consists of 18 items designed to reflect symptoms of ADHD. Each item is scored on a scale of 0 (Never or rarely) to 3 (Very Often). The subscales of the ADHDRS-IV included the Inattention and the hyperactivity/Impulsivity subscales (total possible score range, 0-54). The Inattention subscale consists of the sum of 9 items: 1, 3, 5, 7, 9, 11, 13, 15, and 17. The Hyperactivity/Impulsivity subscale consists of the sum of 9 items: 2, 4, 6, 8, 10, 12, 14, 16, and 18	At baseline, months 1, 2, 3, 4, 6, 9, and 12
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) at Months 1, 2, 3, 4, 6, 9, and 12	CGI-S scale: 1 = Normal, not ill at all; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patients	At baseline, months 1, 2, 3, 4, 6, 9, and 12
Change From Baseline in Clinical Global Impressions-Improvement (CGI-I) at Months 1, 2, 3, 4, 6, 9, and 12	CGI-I scale: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse	At baseline, months 1, 2, 3, 4, 6, 9, and 12

Collaborators and Investigators

• Sponsor: Shionogi

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: July 24, 2008
• First Submitted That Met QC Criteria: July 25, 2008
• First Posted (Estimate): July 28, 2008

Study Record Updates

• Last Update Posted (Actual): April 18, 2018
• Last Update Submitted That Met QC Criteria: April 16, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Attention Deficit Hyperactivity Disorder; CLONICEL; clonidine HCl sustained release
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Disease; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: CLON-303