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CompletedNCT00723190Updated Apr 18, 2018Results posted

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

A Phase 3 interventional study of CLONICEL (Clonidine HCl sustained release) in Attention Deficit Hyperactivity Disorder, sponsored by Shionogi. Completed at 27 sites in United States. Open to participants aged 6 Years to 17 Years. Per ClinicalTrials.gov, last updated 2018-04-18.

Sponsored by Shionogi · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
303
Allocation
Not applicable
Ages
6 Years to 17 Years
Sex
All
01

Study summary

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).

02

Conditions studied

  • Attention Deficit Hyperactivity Disorder

Keywords

  • CLONICEL
  • Attention Deficit Hyperactivity Disorder
  • clonidine HCl sustained release
03

In context

Attention Deficit Disorder with Hyperactivity

1,547 studies on the registry are indexed under Attention Deficit Disorder with Hyperactivity; 254 are open to participants now.

This study's enrollment of 303 is above the median of 71 across 1,233 interventional studies indexed under Attention Deficit Disorder with Hyperactivity.

Browse Attention Deficit Disorder with Hyperactivity studies →

Lead sponsor

Shionogi is the lead sponsor of 105 studies on the registry; 10 are open to participants now.

Of its 39 completed or terminated interventional studies of FDA-regulated products, 21 (54%) have results posted.

Browse Shionogi studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Years to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
303 participants (actual)

Study arms

  • Experimental
    Arm A

    CLONICEL (Clonidine HCl sustained release)

    Drug: CLONICEL (Clonidine HCl sustained release)

Interventions

  • DrugCLONICEL (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

06

What researchers measure

Primary outcomes

  1. 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

    Time frame: 1 year

  2. 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

    Time frame: 1 year

  3. Change From Baseline in 12-lead Electrocardiogram in Terms of QT, QTc Fridericia (QTcF), and QTc Bazett's (QTcB) at Week 4

    Time frame: At baseline and at Week 4

  4. Change From Baseline in Body Weight at Weeks 1, 2, 3, 4, and Months 2, 3, 4, 5, 6, 9, and 12

    Time frame: At baseline and at weeks 1, 2, 3, 4, and months 2, 3, 4, 5, 6, 9, and 12

  5. 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

    Time frame: At baseline and at Week 4

  6. 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

    Time frame: At baseline and at Week 4

  7. 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

    Time frame: At baseline and at Week 4

  8. 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

    Time frame: At baseline and at Week 4

  9. Change From Baseline in 12-lead Electrocardiogram in Terms of Heart Rate at Week 4

    Time frame: At baseline and at Week 4

Secondary outcomes

  1. 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

    Time frame: At baseline, months 1, 2, 3, 4, 6, 9, and 12

  2. 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

    Time frame: At baseline, months 1, 2, 3, 4, 6, 9, and 12

  3. 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

    Time frame: At baseline, months 1, 2, 3, 4, 6, 9, and 12

07

Results

Posted Feb 27, 2012
Limitations and caveats
Efficacy results need to be reviewed in the context that the study is an open-label/non-placebo controlled study. No formal statistical testing of efficacy results has been done. No adjustments have been made to account for drop-outs or missing data.

Participant flow

This was a multicenter study conducted at 27 study centers in the United States. First subject visit was on January 09, 2008 and last subject completed the study on March 08, 2010

Participant flow — Overall Study
MilestoneKAPVAY (CLONICEL)
Started303
Safety population301
Completed161
Not completed142
Withdrew: Withdrawal by subject45
Withdrew: Lost to follow-up37
Withdrew: Adverse event18
Withdrew: Lack of efficacy16
Withdrew: Protocol violation15
Withdrew: Other-premature discontinuation9
Withdrew: Other-not included in safety population2

Outcome measures

PrimarySafety 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

Time frame:
1 year
Reported as:
Number · Participants
Safety Assessment in Terms of Adverse Events (Treatment-emergent [TEAEs] and Serious [SAEs])
ParticipantsKAPVAY (CLONICEL)
Total Safety Population301
Subjects with ≥1 TEAEs246
Subjects with ≥1 related TEAEs178
Subjects with ≥1 SAEs2
Subjects with ≥1 TEAEs leading to discontinuation17
SecondaryChange 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

Time frame:
At baseline, months 1, 2, 3, 4, 6, 9, and 12
Reported as:
Mean · Units on a scale
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
Units on a scaleKAPVAY (CLONICEL)
1-month (n = 229)-13.7 ± 11.52
2-month (n = 221)-14.4 ± 11.73
3-month (n = 203)-14.8 ± 12.55
4-month (n = 142)-16.3 ± 12.59
6-month (n = 184)-14.6 ± 12.04
9-month (n = 119)-18.1 ± 12.66
12-month (n = 98)-14.6 ± 14.05
PrimarySafety 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

Time frame:
1 year
Reported as:
Number · Events
Safety Assessment in Terms of Adverse Events (Treatment-emergent [TEAEs] and Serious [SAEs])
EventsKAPVAY (CLONICEL)
Total number of TEAEs954
Total number of related TEAEs438
Total number of SAEs2
PrimaryChange From Baseline in 12-lead Electrocardiogram in Terms of QT, QTc Fridericia (QTcF), and QTc Bazett's (QTcB) at Week 4
Time frame:
At baseline and at Week 4
Reported as:
Mean · milliseconds
Change From Baseline in 12-lead Electrocardiogram in Terms of QT, QTc Fridericia (QTcF), and QTc Bazett's (QTcB) at Week 4
millisecondsKAPVAY (CLONICEL)
QT17.9 ± 25.69
QTcF1.4 ± 16.42
QTcB-8.0 ± 22.15
PrimaryChange From Baseline in Body Weight at Weeks 1, 2, 3, 4, and Months 2, 3, 4, 5, 6, 9, and 12
Time frame:
At baseline and at weeks 1, 2, 3, 4, and months 2, 3, 4, 5, 6, 9, and 12
Reported as:
Mean · Kilograms
Change From Baseline in Body Weight at Weeks 1, 2, 3, 4, and Months 2, 3, 4, 5, 6, 9, and 12
KilogramsKAPVAY (CLONICEL)
week 1 (n = 283)0.3 ± 2.25
week 2 (n = 283)0.4 ± 2.28
week 3 (n = 278)0.6 ± 2.39
week 4 (n = 269)0.7 ± 2.42
month 2 (n = 246)0.9 ± 2.61
month 3 (n = 232)1.2 ± 2.97
month 4 (n = 212)1.4 ± 3.25
month 5 (n = 47)1.7 ± 5.63
month 6 (n = 204)2.1 ± 3.84
month 9 (n = 123)3.6 ± 3.72
month 12 (n = 123)4.5 ± 4.83
PrimaryChange 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

Time frame:
At baseline and at Week 4
Reported as:
Mean · mmHg
Change From Baseline in Diastolic Blood Pressure at Week 4
mmHgKAPVAY (CLONICEL)
Change From Baseline in Diastolic Blood Pressure at Week 4-4.2 ± 9.13
PrimaryChange 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

Time frame:
At baseline and at Week 4
Reported as:
Mean · mmHg
Change From Baseline in Systolic Blood Pressure at Week 4
mmHgKAPVAY (CLONICEL)
Change From Baseline in Systolic Blood Pressure at Week 4-5.0 ± 10.71
PrimaryChange 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

Time frame:
At baseline and at Week 4
Reported as:
Mean · Fahrenheit
Change From Baseline in Body Temperature at Week 4
FahrenheitKAPVAY (CLONICEL)
Change From Baseline in Body Temperature at Week 4-0.08 ± 0.791
PrimaryChange 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

Time frame:
At baseline and at Week 4
Reported as:
Mean · beats per minute
Change From Baseline in Heart Rate at Week 4
beats per minuteKAPVAY (CLONICEL)
Change From Baseline in Heart Rate at Week 4-7.0 ± 13.59
PrimaryChange From Baseline in 12-lead Electrocardiogram in Terms of Heart Rate at Week 4
Time frame:
At baseline and at Week 4
Reported as:
Mean · beats per minute
Change From Baseline in 12-lead Electrocardiogram in Terms of Heart Rate at Week 4
beats per minuteKAPVAY (CLONICEL)
Change From Baseline in 12-lead Electrocardiogram in Terms of Heart Rate at Week 4-10.6 ± 14.32
SecondaryChange 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

Time frame:
At baseline, months 1, 2, 3, 4, 6, 9, and 12
Reported as:
Mean · Units on a scale
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) at Months 1, 2, 3, 4, 6, 9, and 12
Units on a scaleKAPVAY (CLONICEL)
1-month (n = 229)-1.2 ± 1.17
2-month (n = 220)-1.3 ± 1.12
3-month (n = 202)-1.3 ± 1.29
4-month (n = 143)-1.5 ± 1.19
6-month (n = 185)-1.4 ± 1.15
9-month (n = 119)-1.7 ± 1.35
12-month (n = 97)-1.4 ± 1.46
SecondaryChange 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

Time frame:
At baseline, months 1, 2, 3, 4, 6, 9, and 12
Reported as:
Mean · Units on a scale
Change From Baseline in Clinical Global Impressions-Improvement (CGI-I) at Months 1, 2, 3, 4, 6, 9, and 12
Units on a scaleKAPVAY (CLONICEL)
1-month (n = 229)2.5 ± 1.05
2-month (n = 220)2.5 ± 1.11
3-month (n = 202)2.5 ± 1.10
4-month (n = 143)2.3 ± 1.04
6-month (n = 185)2.4 ± 1.11
9-month (n = 119)2.1 ± 1.11
12-month (n = 97)2.4 ± 1.39

Adverse events

Collected over 1 year. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
KAPVAY (CLONICEL)—2/301 (0.7%)246/301 (81.7%)
Most frequent serious events
Most frequent serious events
EventKAPVAY (CLONICEL)
Suicidal BehaviorPsychiatric disorders1/301
CellulitisInfections and infestations1/301
Most frequent other events
Showing 10 of 29
Most frequent other events
EventKAPVAY (CLONICEL)
SomnolencePsychiatric disorders96/301
HeadacheNervous system disorders49/301
Upper Respiratory Tract InfectionInfections and infestations39/301
Abdominal Pain UpperGastrointestinal disorders37/301
FatigueGeneral disorders37/301
InsomniaNervous system disorders28/301
IrritabilityGeneral disorders28/301
CoughRespiratory, thoracic and mediastinal disorders25/301
Decreased AppetiteMetabolism and nutrition disorders25/301
Body Temperature IncreasedInvestigations22/301

Baseline characteristics

Age, Continuous
Age, Continuous(Years)KAPVAY (CLONICEL)
Mean10.1 ± 2.75
Age, Continuous
Age, Continuous(Years)KAPVAY (CLONICEL)
Median10.0 (6.0 to 17.0)
Age, Customized
Age, Customized(Participants)KAPVAY (CLONICEL)
6-12 Years239
> 12-17 Years62
Sex: Female, Male
Sex: Female, Male(Participants)KAPVAY (CLONICEL)
Female80
Male221
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)KAPVAY (CLONICEL)
White186
Black/African American69
Hispanic or Latino25
Other21
Weight
Weight(Kilograms)KAPVAY (CLONICEL)
Mean42.3 ± 18.94
Weight
Weight(Kilograms)KAPVAY (CLONICEL)
Median38.1 (19.6 to 131.0)
08

Study locations

27 sites
  • Little Rock, Arkansas 72205, United States
  • El Centro, California 92243, United States
  • Irvine, California 92612, United States
  • San Diego, California 92103, United States
  • Bradenton, Florida 34208, United States
  • Gainesville, Florida 32607, United States
  • Jacksonville, Florida 32216, United States
  • Lauderhill, Florida 33319, United States
  • Miami, Florida 33161, United States
  • Orlando, Florida 32806, United States
  • Bardstown, Kentucky 40004, United States
  • Baltimore, Maryland 21208, United States
  • Rochester Hills, Michigan 48307, United States
  • St Louis, Missouri 63005, United States
  • Voorhees Township, New Jersey 08043, United States
  • Willingboro, New Jersey 08046, United States
  • Chapel Hill, North Carolina 27514, United States
  • Charlotte, North Carolina 28209, United States
  • Durham, North Carolina 27705, United States
  • Cleveland, Ohio 44106, United States
  • Oklahoma City, Oklahoma 73103, United States
  • Oklahoma City, Oklahoma 73116, United States
  • Houston, Texas 77007, United States
  • Lake Jackson, Texas 77566, United States
  • Wharton, Texas 77488, United States
  • Clinton, Utah 84015, United States
  • Kirkland, Washington 98033, United States
09

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Jan 2008, a primary completion of Mar 2010 and a completion of Jun 2010. It does not say whether these dates are actual or estimated.

Results were first posted in Feb 2012, 1 year 11 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Jul 24, 2008
First posted
Jul 28, 2008
Start
Jan 2008
Primary completionActual
Mar 2010
CompletionActual
Jun 2010
Results first posted
Feb 27, 2012
Last update
Apr 18, 2018
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 18, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00723190
Lead sponsor
Shionogi
First posted
Jul 28, 2008
Start date
Jan 2008
Primary completion
Mar 2010
Completion
Jun 2010
Results posted
Feb 27, 2012
Last update
Apr 18, 2018

Study contacts

Shionogi Clinical Trials Administrator Clinical Support Help Line
study director · Shionogi

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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