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Trial record 1 of 1 for:    NCT00368069
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A Study to Look at the Efficacy and Safety of Keppra® Extended Release Formulation - XR

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ClinicalTrials.gov Identifier: NCT00368069
Recruitment Status : Completed
First Posted : August 24, 2006
Results First Posted : July 28, 2009
Last Update Posted : August 26, 2015
Sponsor:
Information provided by (Responsible Party):
UCB Pharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Epilepsy
Interventions Drug: Keppra® extended release formulation - XR
Drug: Placebo
Enrollment 158
Recruitment Details The N01235 study began recruitment in August 2006 with study completion occurring in May 2007.
Pre-assignment Details Baseline and Participant Flow data consists of the Intent-to-Treat (ITT) analysis group. The ITT group consists of all randomized subjects.
Arm/Group Title Keppra® Placebo
Hide Arm/Group Description Keppra® extended release formulation (XR) placebo
Period Title: Overall Study
Started 79 79
Completed 71 72
Not Completed 8 7
Reason Not Completed
Adverse Event             5             2
Lack of Efficacy             0             1
Lost to Follow-up             1             0
Protocol Violation             0             2
Withdrawal of Consent             2             1
no blood sampling possible             0             1
Arm/Group Title Keppra® Placebo Total
Hide Arm/Group Description Keppra® extended release formulation (XR) placebo Total of all reporting groups
Overall Number of Baseline Participants 79 79 158
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 79 participants 158 participants
33.97  (13.41) 32.38  (12.60) 33.17  (13.00)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 79 participants 158 participants
Female
27
  34.2%
32
  40.5%
59.0
Male
52
  65.8%
47
  59.5%
99.0
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 79 participants 158 participants
Mexico 15 16 31
Finland 2 2 4
Ukraine 13 12 25
South Africa 4 4 8
Russian Federation 19 19 38
India 25 26 51
Brazil 1 0 1
1.Primary Outcome
Title Partial Onset Seizure (POS) Frequency Per Week - Intention-To-Treat (ITT) Population
Hide Description Number of POS over the treatment period standardized to 1 week period.
Time Frame Treatment period (12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) (Analyses were performed on subjects from the ITT with non-missing information during baseline and treatment period.)
Arm/Group Title Keppra® Placebo
Hide Arm/Group Description:
Keppra® extended release formulation (XR)
placebo
Overall Number of Participants Analyzed 75 78
Least Squares Mean (Standard Error)
Unit of Measure: seizures per week (log-transformed data)
0.912  (0.053) 1.067  (0.052)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Keppra®, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments [Not Specified]
Method ANCOVA
Comments Analysis of covariance (ANCOVA) on (log-) POS freq/week over Treatment period with Treatment, (log-) Baseline POS freq/week as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.155
Confidence Interval 95%
0.009 to 0.301
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Keppra®, Placebo
Comments Treatment difference was assessed through the percent reduction in POS freq/week of Keppra over Placebo by back transformation of the results of the ANCOVA on log data
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Transf. of ANCOVA results on log data
Comments Percent Reduction of Keppra over PBO is calculated based on the ANCOVA on log data as 100*(1-exp(LSmeans Keppra -LSMeans Placebo))
Method of Estimation Estimation Parameter Percent reduction over Placebo
Estimated Value 14.4
Confidence Interval 95%
0.9 to 26.0
Estimation Comments [Not Specified]
2.Primary Outcome
Title Partial Onset Seizure (POS) Frequency Per Week - Per Protocol (PP) Population
Hide Description Number of POS over the treatment period standardized to 1 week period
Time Frame Treatment Period (12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol (PP) Population (Analyses were performed on subjects from the PP Population with non-missing information during both baseline and treatment period)
Arm/Group Title Keppra® Placebo
Hide Arm/Group Description:
Keppra® extended release formulation (XR)
placebo
Overall Number of Participants Analyzed 67 69
Least Squares Mean (Standard Error)
Unit of Measure: seizures per week (log-transformed data)
0.914  (0.049) 1.119  (0.048)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Keppra®, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA on (log-) Treatment POS frequency per week with Treatment and (log-) Baseline POS frequency per week as covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.205
Confidence Interval 95%
0.070 to 0.341
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Keppra®, Placebo
Comments Treatment difference was assessed through the percent reduction in POS frequency per week of Keppra over Placebo by back transformation of the results of the ANCOVA on log data
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Transf. of ANCOVA results on log data
Comments Percent Reduction of Keppra over Placebo is calculated based on the ANCOVA on log data as 100*(1-exp(LSmeans Keppra -LSMeans Placebo))
Method of Estimation Estimation Parameter Percent reduction over Placebo
Estimated Value 18.6
Confidence Interval 95%
6.7 to 28.9
Estimation Comments [Not Specified]
3.Secondary Outcome
Title POS Seizure Frequency Per Week Over Baseline and Treatment Period
Hide Description [Not Specified]
Time Frame Baseline Period (8 weeks) - Treatment Period (12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population - no imputation techniques used for missing data (number of subjects with non-missing data for Baseline = ITT Population and for Treatment period = 75 patients for Levetiractam and 78 patients for PBO) Clusters of type I count are included in the count of Type I seizures
Arm/Group Title Keppra® Placebo
Hide Arm/Group Description:
Keppra® extended release formulation (XR)
placebo
Overall Number of Participants Analyzed 79 79
Median (Inter-Quartile Range)
Unit of Measure: seizures per week
Baseline POS frequency per week
1.80
(1.13 to 4.13)
2.11
(1.33 to 3.26)
Treatment POS frequency per week
0.99
(0.33 to 2.70)
1.36
(0.92 to 2.85)
4.Secondary Outcome
Title All (Type I+II+III) Seizures Frequency Per Week
Hide Description Number of All type Seizures over the treatment period standardized to 1 week period (Type I -Partial Onset Seizures, Type II - Generalized Seizures, Type III - Unclassified Epileptic Seizures)
Time Frame Treatment period (12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT (Analyses were performed on subjects from the ITT with non-missing information during baseline and treatment period.)
Arm/Group Title Keppra® Placebo
Hide Arm/Group Description:
Keppra® extended release formulation (XR)
placebo
Overall Number of Participants Analyzed 75 78
Least Squares Mean (Standard Error)
Unit of Measure: seizures per week (log-transformed data)
0.928  (0.053) 1.086  (0.052)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Keppra®, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA on (log-) seizure frequency per week over Treatment period with Treatment, (log-) Baseline seizure frequency per week as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.158
Confidence Interval 95%
0.012 to 0.305
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Keppra®, Placebo
Comments Treatment difference was assessed through the percent reduction in POS frequency per week of Keppra over Placebo by back transformation of the results of the ANCOVA on log data
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Transf. of ANCOVA results on log data
Comments Percent Reduction of Keppra over Placebo is calculated based on the ANCOVA on log data as 100*(1-exp(LSmeans Keppra -LSMeans Placebo))
Method of Estimation Estimation Parameter Percent reduction over Placebo
Estimated Value 14.7
Confidence Interval 95%
1.2 to 26.3
Estimation Comments [Not Specified]
5.Secondary Outcome
Title 50% Response in Weekly POS Frequency
Hide Description A subject is considered as a 50% responder in POS if he/she has a >= 50% decrease from Baseline in the POS frequency/week over Treatment period.
Time Frame Treatment period (12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Based on the number of evaluable patients. A patient is considered as evaluable for the response status if he has seizure information in at least one of the periods (baseline or treatment period)
Arm/Group Title Keppra® Placebo
Hide Arm/Group Description:
Keppra® extended release formulation (XR)
placebo
Overall Number of Participants Analyzed 79 79
Measure Type: Number
Unit of Measure: Participants
Response 34 23
Non-Response 45 56
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Keppra®, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.070
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression analysis including Treatment as a factor.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.84
Confidence Interval 95%
0.95 to 3.55
Estimation Comments Based on the number of evaluable patients. A patient is considered as evaluable for the response status if he has seizure information in at least one of the period (baseline or treatment period.
6.Secondary Outcome
Title Response in Weekly POS Frequency (Categorized Into 6 Categories According to Reduction) Over the Treatment Period of 12 Weeks
Hide Description The response is classified according to the percent reduction from baseline in the POS frequency per week over the Treatment Period of 12 weeks duration.
Time Frame over the treatment period (12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Based on the number of evaluable patients. A patient is considered as evaluable for the response status if he has seizure information in at least one of the periods (baseline or treatment period).
Arm/Group Title Keppra® Placebo
Hide Arm/Group Description:
Keppra® extended release formulation (XR)
placebo
Overall Number of Participants Analyzed 79 79
Measure Type: Number
Unit of Measure: Participants
< -25% 11 13
-25% - <25% 14 23
25% - <75% 35 34
75% - <100% 11 7
100% 8 2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Keppra®, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method Mantel Haenszel
Comments Subjects with missing data during the Treatment period were considered in the category <-25%.
Time Frame Adverse Events were collected from Selection Visit (Week 0) until Final Visit (Week 22).
Adverse Event Reporting Description Adverse Event reporting is data is taken from the Safety Set (SS) analysis group. The SS is comprised all subjects who were dispensed study medication.
 
Arm/Group Title Keppra® Placebo
Hide Arm/Group Description Keppra® extended release formulation (XR) placebo
All-Cause Mortality
Keppra® Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Keppra® Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/77 (7.79%)      2/79 (2.53%)    
Injury, poisoning and procedural complications     
Concussion * 1  1/77 (1.30%)  1 0/79 (0.00%)  0
Nervous system disorders     
Epilepsy * 1  1/77 (1.30%)  1 1/79 (1.27%)  1
Ischaemic stroke * 1  1/77 (1.30%)  1 0/79 (0.00%)  0
Partial seizures with secondary generalisation * 1  0/77 (0.00%)  0 1/79 (1.27%)  1
Simple partial seizures * 1  1/77 (1.30%)  1 0/79 (0.00%)  0
Stupor * 2  0/77 (0.00%)  0 1/79 (1.27%)  1
Respiratory, thoracic and mediastinal disorders     
Respiratory failure * 1  1/77 (1.30%)  1 0/79 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash * 1  1/77 (1.30%)  1 0/79 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 9.0
2
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Keppra® Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/77 (29.87%)      21/79 (26.58%)    
Gastrointestinal disorders     
Nausea * 1  4/77 (5.19%)  5 2/79 (2.53%)  2
General disorders     
Irritability * 1  5/77 (6.49%)  5 0/79 (0.00%)  0
Infections and infestations     
Influenza * 1  6/77 (7.79%)  7 3/79 (3.80%)  3
Nasopharyngitis * 1  5/77 (6.49%)  6 4/79 (5.06%)  4
Nervous system disorders     
Dizziness * 1  4/77 (5.19%)  4 2/79 (2.53%)  2
Headache * 1  5/77 (6.49%)  8 11/79 (13.92%)  21
Somnolence * 1  6/77 (7.79%)  7 2/79 (2.53%)  2
*
Indicates events were collected by non-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.
UCB has > 60 days but <= 180 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB Clinical Trial Call Center
Organization: UCB Pharma
Phone: +1 877 822 9493
Layout table for additonal information
Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT00368069    
Other Study ID Numbers: N01235
Eudra CT# 2006-000987-10
First Submitted: August 11, 2006
First Posted: August 24, 2006
Results First Submitted: April 1, 2009
Results First Posted: July 28, 2009
Last Update Posted: August 26, 2015