Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 25 of 326 for:    clonidine

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01439126
Recruitment Status : Completed
First Posted : September 22, 2011
Results First Posted : October 15, 2014
Last Update Posted : October 27, 2014
Sponsor:
Information provided by (Responsible Party):
Concordia Pharmaceuticals Inc., Barbados

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Attention Deficit Hyperactivity Disorder
Interventions Drug: clonidine hydrochloride
Drug: Placebo
Enrollment 135
Recruitment Details The study was conducted at 34 sites in the US. First patient was enrolled on September 8, 2011 and last patient completed on October 29, 2012
Pre-assignment Details The study population included male or female subjects 6 to 17 years of age, who met the Diagnostic and Statistical Manual of Mental Disorders 4th Edition Text Revision (DSM-IV-TR) criteria for Attention Deficit Hyperactivity Disorder (ADHD).
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Hide Arm/Group Description

Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period.

All subjects were given study medication at the baseline visit (Visit 2, open label) and instructed to take 1 x 0.1 mg tablet each evening (Day 1) at bedtime until the next visit. Subjects who required an increase in total dose to 0.2 mg/day took 1 x 0.1 mg tablet (0.1 mg) in the morning and at bedtime until the next visit. Those who required a further increase in dose to 0.3 mg/day took 1 x 0.1 mg tablet in the morning and 2 x 0.1 mg tablets at bedtime until the next visit. Patient increasing dose to 0.4 mg/day were instructed to take 2 x 0.1 mg tablets in the morning and at bedtime until the next visit.

Of 68 Subjects randomized to KAPVAY:

24 (35.3%) oral dose of 0.4 mg/day 25 (36.8%) oral dose of 0.3 mg/day 14 (20.6%) oral dose of 0.2 mg/day 5 (7.4%) oral dose of 0.1 mg/day

Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study

Of 67 Subjects randomized to Placebo:

26 (38.8%) oral dose of 0.4 mg/day 24 (35.8%) oral dose of 0.3 mg/day 15 (22.4%) oral dose of 0.2 mg/day 2 (3.0%) oral dose of 0.1 mg/day

Period Title: Overall Study
Started 68 67
Completed 37 25
Not Completed 31 42
Reason Not Completed
Adverse Event             2             0
Withdrawal by Subject             5             21
Protocol Violation             6             4
Lost to Follow-up             6             3
Other-Use of prohibited treatment             0             2
Other-Miscellaneous             12             12
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo Total
Hide Arm/Group Description Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study Total of all reporting groups
Overall Number of Baseline Participants 68 67 135
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 68 participants 67 participants 135 participants
10.7  (2.77) 10.9  (2.98) 10.8  (2.88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 67 participants 135 participants
Female
25
  36.8%
16
  23.9%
41
  30.4%
Male
43
  63.2%
51
  76.1%
94
  69.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 67 participants 135 participants
Hispanic or Latino
12
  17.6%
20
  29.9%
32
  23.7%
Not Hispanic or Latino
56
  82.4%
47
  70.1%
103
  76.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 67 participants 135 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   1.5%
0
   0.0%
1
   0.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
23
  33.8%
14
  20.9%
37
  27.4%
White
37
  54.4%
50
  74.6%
87
  64.4%
More than one race
7
  10.3%
3
   4.5%
10
   7.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 68 participants 67 participants 135 participants
40.49  (15.721) 41.61  (16.978) 41.05  (16.350)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 68 participants 67 participants 135 participants
145.64  (17.737) 145.45  (17.928) 145.55  (17.833)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 68 participants 67 participants 135 participants
18.29  (2.921) 18.79  (3.485) 18.54  (3.203)
1.Primary Outcome
Title 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
Hide Description

Treatment failure a ≥30 percentage increase (worsening)(ADHD-RS-IV, clinician version) total score and a ≥2 point increase (worsening) in Clinical Global Impressions-Severity of Illness Scale (CGI-S) at any two consecutive visits during the randomized-withdrawal period.

The ADHD-RS-IV of 2 subscales: inattention - 9 items and hyperactivity-impulsivity - 9 items. Each gives a score ranging from 0 (none, never or rarely) to 3 (severe, very often), for a total score ranging from 0 to 54 (higher score worse).

The CGI-S is a 7-point scale,1 (Normal, not at all ill) to 7 (extremely ill patients).The CGI-Severity (CGI-S) asks the clinician one question: “Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?” which is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.

Time Frame From randomization to end of the randomized-withdrawal period (26 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Full Analysis Set. This set included all randomized subjects who took at least 1 dose of study medication during the double blind (randomized-withdrawal) phase
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Hide Arm/Group Description:
Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period
Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study
Overall Number of Participants Analyzed 68 67
Measure Type: Number
Unit of Measure: % of Participants
31 42
2.Secondary Outcome
Title 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
Hide Description 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
Time Frame Time From randomization to treatment failure (up to 26 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Full Analysis Set
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Hide Arm/Group Description:
Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period
Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study
Overall Number of Participants Analyzed 68 67
Median (95% Confidence Interval)
Unit of Measure: days
212 [1] 
(84 to NA)
75
(36 to 154)
[1]
NA implies the median or the one or both limits in the confidence interval could not be estimated.
3.Secondary Outcome
Title 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)
Hide Description 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. The ADHD-RS-IV of 2 subscales: inattention - 9 items and hyperactivity-impulsivity - 9 items. Each gives a score ranging from 0 (none, never or rarely) to 3 (severe, very often), for a total score ranging from 0 to 54 (higher score worse and a lower score more favourable). Two subscales are summed.
Time Frame From randomization to end of the randomized-withdrawal period (26 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Full Analysis Set
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Hide Arm/Group Description:
Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period
Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study
Overall Number of Participants Analyzed 68 67
Mean (Standard Deviation)
Unit of Measure: scores on a scale
3.0  (10.75) 7.0  (12.30)
4.Secondary Outcome
Title 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)
Hide Description

The CGI-S is a clinician rated instrument designed to assess the subject’s current illness state. The CGI-Severity (CGI-S) asks the clinician one question: “Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?” which is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.

This rating is based upon observed and reported symptoms, behavior, and function in the past seven days.

Time Frame From randomization to end of the randomized-withdrawal period (26 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Full Analysis Set
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Hide Arm/Group Description:
Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period
Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study
Overall Number of Participants Analyzed 68 67
Mean (Standard Deviation)
Unit of Measure: scores on a scale
0.4  (1.20) 0.9  (1.28)
5.Secondary Outcome
Title 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)
Hide Description The WFIRS-P is designed to assess the impact of child’s behavior or emotional problems on 7 domains related to function: Family (10 items), School Learning (4 items), School Behavior (6 items), Life Skills (10 items), Child’s Self-concept (3 items), Social Activities (7 items), and Risky Activities (10 items). Each item was scored on a scale ranging from 0 (“never" or "not at all”) to 3 (“very often" or "very much”). Each scale score was calculated as the average for that scale. The total score is the average of all non-missing items. Higher scores are associated with greater impact of disease on functioning.
Time Frame From randomization to end of the randomized-withdrawal period (26 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Full Analysis Set
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Hide Arm/Group Description:
Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period
Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study
Overall Number of Participants Analyzed 68 67
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.0  (0.34) 0.0  (0.38)
6.Secondary Outcome
Title 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)
Hide Description

Change in the ESS-C scale from randomization to end of randomized-withdrawal period. The ESS-C is a simple eight-tem Likert scale designed to assess daytime sleepiness in children aged 2-18 years. 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.

The ESS-C comprises 8 items describing various daytime activities. Item scores ranging from 0 (“would never doze or sleep”) to 3 (“high chance of dozing or sleeping”). A total score is derived as the sum of the items, with higher total scores indicative of a greater level of sleepiness (worse outcome). Total scores range from 0 to 24.

Time Frame From randomization to end of the randomized-withdrawal period (26 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Full Analysis Set
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Hide Arm/Group Description:
Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period
Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study
Overall Number of Participants Analyzed 68 67
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.6  (3.18) -0.6  (4.09)
7.Secondary Outcome
Title Long-term Safety of KAPVAY in Children and Adolescents With ADHD Based on the Assessment of Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Study Drug Discontinuation, Clinically Significant Changes or Abnormalities in Vital Signs
Hide Description [Not Specified]
Time Frame From study start to study end (40 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Full Analysis Set
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Hide Arm/Group Description:
Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period
Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study
Overall Number of Participants Analyzed 68 67
Measure Type: Number
Unit of Measure: Participants
No. Subjects with At Least 1 Treatment-Emergent AE 34 31
Any Severe Treatment-Emergent AE (TEAE) 2 0
Any SAE 0 2
Treatment Emergent AE leading to discontinuation 2 0
Any Treatment-Related AE 18 12
Vital Signs Abnormalities 3 1
8.Secondary Outcome
Title Long-term Safety of KAPVAY in Children and Adolescents With ADHD Based on the Assessment of Changes in the Columbia Suicide Severity Rating Scale (C-SSRS)
Hide Description

The outcome reported is the number of subjects that responded "Yes" to the question “Do you have a wish to be dead” at Visit 20.

C-SSRS is a clinician-rated instrument designed to provide consistent and systematic assessment of both suicidal ideation and behavior within a study, as well as across studies. The scale is a feasible, low burden series of questions that appropriately assess and track all suicidal events, including ideation. Suicidal ideation is assessed according to yes/no responses to 5 questions of increasing severity (from a wish to die to an active thought of killing oneself with plan and intent) as follows:

  1. Wish to be Dead
  2. Non-Specific Active Suicidal Thoughts
  3. Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act
  4. Active Suicidal Ideation with Some Intent to Act, without Specific Plan
  5. Active Suicidal Ideation with Specific Plan and Intent
Time Frame Visit 20 (Week 40)
Hide Outcome Measure Data
Hide Analysis Population Description
Double-Blind Full Analysis Set
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Hide Arm/Group Description:
Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period
Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study
Overall Number of Participants Analyzed 68 67
Measure Type: Number
Unit of Measure: participants
0 1
Time Frame Throughout the study
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Hide Arm/Group Description Subjects in the KAPVAY arm received their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) for the duration of the 26-week randomized-withdrawal period Subjects randomized to the placebo arm were tapered off their optimal dose of KAPVAY (as determined after a 4-week, open-label, dose optimization period) at weekly intervals in decrements of 0.1 mg/day until reaching the dose of 0 mg/day, and then received only placebo for the rest of the study
All-Cause Mortality
Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/68 (0.00%)   2/67 (2.99%) 
Blood and lymphatic system disorders     
Sickle cell anemia with crisis  1  0/68 (0.00%)  1/67 (1.49%) 
Psychiatric disorders     
Suicidal ideation  1  0/68 (0.00%)  1/67 (1.49%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Subjects on KAPVAY (Clonidine Hydrochloride) Subjects on Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   15/68 (22.06%)   7/67 (10.45%) 
Gastrointestinal disorders     
Abdominal pain upper  1  1/68 (1.47%)  1/67 (1.49%) 
General disorders     
Fatigue  1  1/68 (1.47%)  0/67 (0.00%) 
Investigations     
Electrocardiogram QT  1  2/68 (2.94%)  0/67 (0.00%) 
Weight increased  1  2/68 (2.94%)  0/67 (0.00%) 
Nervous system disorders     
Somnolence  1  3/68 (4.41%)  0/67 (0.00%) 
Headache  1  2/68 (2.94%)  3/67 (4.48%) 
Sedation  1  1/68 (1.47%)  1/67 (1.49%) 
Dizziness postural  1  2/68 (2.94%)  2/67 (2.99%) 
Psychiatric disorders     
Affect lability  1  1/68 (1.47%)  0/67 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John AR McCleery, CPA, CA, Managing Director and CFO
Organization: Concordia Pharmaceuticals Inc.
Phone: 1-246-256-1861
EMail: jmccleery@concordiarx.com
Layout table for additonal information
Responsible Party: Concordia Pharmaceuticals Inc., Barbados
ClinicalTrials.gov Identifier: NCT01439126     History of Changes
Other Study ID Numbers: SHN-KAP-401
First Submitted: September 13, 2011
First Posted: September 22, 2011
Results First Submitted: June 18, 2013
Results First Posted: October 15, 2014
Last Update Posted: October 27, 2014