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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: CLONICEL (Clonidine HCl sustained release)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>CLONICEL (Clonidine HCl sustained release) | Drug: CLONICEL (Clonidine HCl sustained release)<br>* 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<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLONICEL, Attention Deficit Hyperactivity Disorder, clonidine HCl sustained release