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Clobazam in Subjects With Lennox-Gastaut Syndrome

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ClinicalTrials.gov Identifier: NCT00162981
Recruitment Status : Completed
First Posted : September 13, 2005
Results First Posted : February 9, 2012
Last Update Posted : February 9, 2012
Sponsor:
Information provided by (Responsible Party):
Lundbeck LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Epilepsy
Epilepsy, Generalized
Seizures
Interventions Drug: Clobazam Low Dose
Drug: Clobazam High Dose
Enrollment 68
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Clobazam Low Dose Clobazam High Dose
Hide Arm/Group Description 5 to 10 mg/day with doses in the morning and at bedtime; orally 5 to 40 mg/day with doses in the morning and at bedtime; orally
Period Title: Overall Study
Started 32 36
Completed 28 30
Not Completed 4 6
Reason Not Completed
Adverse Event             2             5
Withdrawal by Subject             1             1
Physician Decision             1             0
Arm/Group Title Clobazam Low Dose Clobazam High Dose Total
Hide Arm/Group Description 5 to 10 mg/day with doses in the morning and at bedtime; orally 5 to 40 mg/day with doses in the morning and at bedtime; orally Total of all reporting groups
Overall Number of Baseline Participants 32 36 68
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 36 participants 68 participants
<=18 years
30
  93.8%
33
  91.7%
63
  92.6%
Between 18 and 65 years
2
   6.3%
3
   8.3%
5
   7.4%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 36 participants 68 participants
9.18  (5.37) 8.51  (5.14) 8.82  (5.22)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 36 participants 68 participants
Female
13
  40.6%
13
  36.1%
26
  38.2%
Male
19
  59.4%
23
  63.9%
42
  61.8%
1.Primary Outcome
Title Percent Reduction in Number of Drop Seizures.
Hide Description Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
Time Frame 4-week baseline period and 4-week maintenance period
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intention-to-Treat (MITT) populations consist of all randomized patients who received study medication and who have both a baseline and post-baseline measurement and have at least one measurement during the maintenance period.
Arm/Group Title Clobazam Low Dose Clobazam High Dose
Hide Arm/Group Description:
5 to 10 mg/day with doses in the morning and at bedtime; orally
5 to 40 mg/day with doses in the morning and at bedtime; orally
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: Percent Reduction
10.1  (122.3) 85.2  (17.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clobazam Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0182
Comments [Not Specified]
Method 1-sided Wilcoxon signed rank test
Comments 1-sided Wilcoxon signed rank test was used to assess the difference from baseline.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Clobazam High Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments 1-sided Wilcoxon signed rank test was used to assess the difference from baseline.
Method 1-sided Wilcoxon signed rank test
Comments [Not Specified]
2.Primary Outcome
Title A Comparison of the High Dose Group to Low Dose Group of the Percent Reduction in Number of Drop Seizures.
Hide Description Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
Time Frame 4-week baseline period and the 4-week maintenance period
Hide Outcome Measure Data
Hide Analysis Population Description
MITT population
Arm/Group Title Clobazam Low Dose Clobazam High Dose
Hide Arm/Group Description:
5 to 10 mg/day with doses in the morning and at bedtime; orally
5 to 40 mg/day with doses in the morning and at bedtime; orally
Overall Number of Participants Analyzed 29 32
Median (Full Range)
Unit of Measure: Percent Reduction
29
(-531 to 100)
93
(48 to 100)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clobazam Low Dose, Clobazam High Dose
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Assuming a standard deviation of 50%, one-tailed significance at 0.05 and a power of 80% to detect a reduction of at least 25% (baseline to final in a within-subjects design), then approximately 27 subjects would have been required in each treatment arm. Assuming a 10% drop-out rate, then approximately 30 subjects per treatment were to be enrolled in the study.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method 1-sided Wilcoxon Rank-Sum Test
Comments 1-sided Wilcoxon Rank-Sum Test was used to compare the high dose group to the low dose group.
3.Secondary Outcome
Title Percent of Patients Considered Treatment Responders Defined as Those With a >= 25%, >= 50%, >= 75%, and 100% Reduction in Drop Seizures.
Hide Description Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.
Time Frame 4-week baseline period and 4-week maintenance period
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Clobazam Low Dose Clobazam High Dose
Hide Arm/Group Description:
5 to 10 mg/day with doses in the morning and at bedtime; orally
5 to 40 mg/day with doses in the morning and at bedtime; orally
Overall Number of Participants Analyzed 32 36
Measure Type: Number
Unit of Measure: Percent of participants
≥ 25% reduction 18 32
≥ 50% reduction 12 30
≥ 75% reduction 7 23
100% reduction 2 8
4.Secondary Outcome
Title Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.
Hide Description The parent/caregiver was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life since the beginning of clobazam treatment by checking "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", or "very much worse".
Time Frame Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
MITT population, baseline evaluations compared to Week 3 evaluations.
Arm/Group Title Clobazam Low Dose Clobazam High Dose
Hide Arm/Group Description:
5 to 10 mg/day with doses in the morning and at bedtime; orally
5 to 40 mg/day with doses in the morning and at bedtime; orally
Overall Number of Participants Analyzed 32 36
Measure Type: Number
Unit of Measure: participants
Very Much Improved 7 15
Much Improved 9 15
Minimally Improved 9 1
No Change 3 0
Minimally Worse 0 1
Much Worse 1 0
Very Much Worse 0 0
5.Secondary Outcome
Title Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.
Hide Description The parent/caregiver was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life since the beginning of clobazam treatment by checking "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", or "very much worse".
Time Frame Week 7
Hide Outcome Measure Data
Hide Analysis Population Description
MITT population, baseline evaluations compared to Week 7 evaluations.
Arm/Group Title Clobazam Low Dose Clobazam High Dose
Hide Arm/Group Description:
5 to 10 mg/day with doses in the morning and at bedtime; orally
5 to 40 mg/day with doses in the morning and at bedtime; orally
Overall Number of Participants Analyzed 32 36
Measure Type: Number
Unit of Measure: participants
Very Much Improved 6 16
Much Improved 6 11
Minimally Improved 10 1
No Change 5 0
Minimally Worse 1 1
Much Worse 0 0
Very Much Worse 0 0
Time Frame Up to 15 weeks
Adverse Event Reporting Description Adverse Events were assessed by the Investigator at the end of the 4 week Baseline period (Day -1) and at weekly/biweekly visits (Weeks 1, 2, 3, 5, 7, 9 and 11) throughout the study.
 
Arm/Group Title Clobazam Low Dose Clobazam High Dose
Hide Arm/Group Description 5 to 10 mg/day with doses in the morning and at bedtime; orally 5 to 40 mg/day with doses in the morning and at bedtime; orally
All-Cause Mortality
Clobazam Low Dose Clobazam High Dose
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Clobazam Low Dose Clobazam High Dose
Affected / at Risk (%) Affected / at Risk (%)
Total   1/32 (3.13%)   3/36 (8.33%) 
Gastrointestinal disorders     
Constipation  1  0/32 (0.00%)  1/36 (2.78%) 
General disorders     
Pyrexia  1  0/32 (0.00%)  1/36 (2.78%) 
Respiratory, thoracic and mediastinal disorders     
Aspiration  1  0/32 (0.00%)  1/36 (2.78%) 
Sleep Apnea Syndrome  1  1/32 (3.13%)  0/36 (0.00%) 
Respiratory Distress  1  0/32 (0.00%)  1/36 (2.78%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Clobazam Low Dose Clobazam High Dose
Affected / at Risk (%) Affected / at Risk (%)
Total   27/32 (84.38%)   31/36 (86.11%) 
Gastrointestinal disorders     
Constipation  1  1/32 (3.13%)  3/36 (8.33%) 
Salivary hypersecretion  1  2/32 (6.25%)  3/36 (8.33%) 
Toothache  1  2/32 (6.25%)  0/36 (0.00%) 
Vomiting  1  0/32 (0.00%)  2/36 (5.56%) 
General disorders     
Irritability  1  1/32 (3.13%)  2/36 (5.56%) 
Pyrexia  1  1/32 (3.13%)  2/36 (5.56%) 
Infections and infestations     
Gastroenteritis viral  1  3/32 (9.38%)  0/36 (0.00%) 
Nasopharyngitis  1  0/32 (0.00%)  4/36 (11.11%) 
Otitis media  1  4/32 (12.50%)  0/36 (0.00%) 
Pneumonia  1  0/32 (0.00%)  2/36 (5.56%) 
Sinusitis  1  2/32 (6.25%)  2/36 (5.56%) 
Upper respiratory tract infection  1  3/32 (9.38%)  1/36 (2.78%) 
Viral infection  1  0/32 (0.00%)  4/36 (11.11%) 
Viral upper respiratory tract infection  1  2/32 (6.25%)  1/36 (2.78%) 
Injury, poisoning and procedural complications     
Contusion  1  2/32 (6.25%)  0/36 (0.00%) 
Skin laceration  1  2/32 (6.25%)  2/36 (5.56%) 
Nervous system disorders     
Convulsion  1  3/32 (9.38%)  1/36 (2.78%) 
Coordination abnormal  1  2/32 (6.25%)  2/36 (5.56%) 
Lethargy  1  3/32 (9.38%)  4/36 (11.11%) 
Sedation  1  2/32 (6.25%)  3/36 (8.33%) 
Somnolence  1  4/32 (12.50%)  7/36 (19.44%) 
Psychiatric disorders     
Abnormal Behavior  1  0/32 (0.00%)  2/36 (5.56%) 
Aggression  1  2/32 (6.25%)  3/36 (8.33%) 
Hypomania  1  1/32 (3.13%)  3/36 (8.33%) 
Insomnia  1  1/32 (3.13%)  3/36 (8.33%) 
Affect lability  1  2/32 (6.25%)  0/36 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.0)
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.
Principal Investigator agrees to delete, at Sponsor’s request, from any proposed Public Presentation any information or material that Sponsor deems confidential or proprietary.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Email contact via H. Lundbeck A/S
Organization: Lundbeck LLC
EMail: LundbeckClinicalTrials@lundbeck.com
Layout table for additonal information
Responsible Party: Lundbeck LLC
ClinicalTrials.gov Identifier: NCT00162981     History of Changes
Other Study ID Numbers: 13108A
OV1002 ( Other Identifier: Former study ID )
First Submitted: September 9, 2005
First Posted: September 13, 2005
Results First Submitted: November 7, 2011
Results First Posted: February 9, 2012
Last Update Posted: February 9, 2012