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Levetiracetam Versus Oxcarbazepine as Monotherapy to Evaluate Efficacy and Safety in Subjects With Newly or Recently Diagnosed Partial Epilepsy (OPTIMAL)

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ClinicalTrials.gov Identifier: NCT01498822
Recruitment Status : Completed
First Posted : December 23, 2011
Results First Posted : August 20, 2015
Last Update Posted : August 20, 2015
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( Korea UCB Co., Ltd. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Epilepsy
Interventions Drug: Levetiracetam
Drug: Oxcarbazepine
Enrollment 353
Recruitment Details This study started to enroll subjects in June 2011. A total of 27 investigators enrolled 353 subjects at 23 sites in Korea.
Pre-assignment Details Participant Flow refers to the Randomized Set, consisting of all subjects who were randomized in this study.
Arm/Group Title Levetiracetam Oxcarbazepine
Hide Arm/Group Description

Levetiracetam twice a day treatment Group

250 mg and 500 mg Levetiracetam tablet, 1000 mg-3000 mg/day, maximum 50 weeks including initial up titration of 500 mg/day for 2 weeks

Oxcarbazepine twice a day treatment Group

150 mg and 300 mg Oxcarbazepine tablet, 900 mg-2400 mg/day, maximum 50 weeks including 2 weeks of up titration (300 mg/day 1 week then 600 mg/day 1 week)

Period Title: Overall Study
Started 175 178
Completed 121 122
Not Completed 54 56
Reason Not Completed
Protocol Violation             8             4
Other Reason             5             2
Lack of Efficacy             7             2
AE, non-serious non-fatal             8             17
SAE, non-fatal             2             2
Adverse Event, serious fatal             1             1
Withdrawal by Subject             15             25
Lost to Follow-up             8             3
Arm/Group Title Levetiracetam Oxcarbazepine Total Title
Hide Arm/Group Description

Levetiracetam twice a day treatment Group

250 mg and 500 mg Levetiracetam tablet, 1000 mg-3000 mg/day, maximum 50 weeks including initial up titration of 500 mg/day for 2 weeks

Oxcarbazepine twice a day treatment Group

150 mg and 300 mg Oxcarbazepine tablet, 900 mg-2400 mg/day, maximum 50 weeks including 2 weeks of up titration (300 mg/day 1 week then 600 mg/day 1 week)

[Not Specified]
Overall Number of Baseline Participants 175 178 353
Hide Baseline Analysis Population Description
Baseline Characteristics refer to the Randomized Set, consisting of all subjects who were randomized in this study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 175 participants 178 participants 353 participants
<=18 years
14
   8.0%
13
   7.3%
27
   7.6%
Between 18 and 65 years
145
  82.9%
143
  80.3%
288
  81.6%
>=65 years
16
   9.1%
22
  12.4%
38
  10.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 175 participants 178 participants 353 participants
39.5  (16.7) 42.7  (17.3) 41.1  (17.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 175 participants 178 participants 353 participants
Female
84
  48.0%
79
  44.4%
163
  46.2%
Male
91
  52.0%
99
  55.6%
190
  53.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 175 participants 178 participants 353 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
174
  99.4%
178
 100.0%
352
  99.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
1
   0.6%
0
   0.0%
1
   0.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Percentage of Subjects With a Treatment Failure
Hide Description Treatment failure is defined as (1) Dropout due to related intolerable adverse event, lack of efficacy or need for addition of another Antiepileptic Drug (AED), or (2) need of a 1-step down-Titration, within 50 weeks from the first dose of study medication.
Time Frame Week 0 (First Dose) to Week 50
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS) consisted of all subjects who received at least 1 (partial) dose of study mediaction, returned at least 1 post-Baseline seizure diary and had no important protocol deviations. Subjects who discontinued the study before Week 50 for any reason other than treatment failure were excluded from the PPS.
Arm/Group Title Per Protocol Set (LEV Treated Subjects) Per Protocol Set (OXC Treated Subjects)
Hide Arm/Group Description:
250 mg and 500 mg Levetiracetam tablet, 1000 mg-3000 mg/day, maximum 50 weeks including initial up titration of 500 mg/day for 2 weeks
150 mg and 300 mg Oxcarbazepine tablet, 900 mg-2400 mg/day, maximum 50 weeks including 2 weeks of up titration (300 mg/day 1 week then 600 mg/day 1 week)
Overall Number of Participants Analyzed 118 128
Measure Type: Number
Unit of Measure: percentage of subjects
12.7 23.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Per Protocol Set (LEV Treated Subjects), Per Protocol Set (OXC Treated Subjects)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The primary analysis of this study aimed to demonstrate that LEV was noninferior to OXC with respect to the treatment failure rate in the Per Protocol Set. The noninferiority margin was 15 %.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Wald methodology
Comments [Not Specified]
Method of Estimation Estimation Parameter Absolut difference
Estimated Value -10.7
Confidence Interval (2-Sided) 95%
-20.2 to -1.2
Estimation Comments Absolute difference in treatment failure rates of LEV versus OXC is defined as "Treatment Failure Rate LEV" minus "Treatment Failure Rate OXC".
2.Secondary Outcome
Title Time to the First Seizure Defined as the Time From the First Dose of Medication to the Occurrence of the First Seizure During the 48 Weeks Treatment Period
Hide Description [Not Specified]
Time Frame From Week 2 to Week 50 (During Treatment Period )
Hide Outcome Measure Data
Hide Analysis Population Description

The Full Analysis Set (FAS) consisted of all subjects who received at least 1 (partial) dose of study mediaction and returned at least 1 post-Baseline seizure diary.

A randomized subject was only excluded from the FAS when there was clear evidence that the subject did not take any study medication.

Arm/Group Title Full Analysis Set (LEV Treated Subjects) Full Analysis Set (OXC Treated Subjects)
Hide Arm/Group Description:
250 mg and 500 mg Levetiracetam tablet, 1000 mg-3000 mg/day, maximum 50 weeks including initial up titration of 500 mg/day for 2 weeks
150 mg and 300 mg Oxcarbazepine tablet, 900 mg-2400 mg/day, maximum 50 weeks including 2 weeks of up titration (300 mg/day 1 week then 600 mg/day 1 week)
Overall Number of Participants Analyzed 173 171
Median (Full Range)
Unit of Measure: months
7.556 [1] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
Dispersion measures for this statistic were not part of the analysis (or it’s specification).
[2]
Kaplan-Meier estimation of percentage of event-free subjects does not fall to or below 50 %, therefore no median time to event could be estimated for the OXC group.
3.Secondary Outcome
Title Percentage of Subjects Who Achieved Seizure Freedom for 24 Consecutive Weeks During the 48 Weeks Treatment Period at Any Time
Hide Description 24-week Seizure Freedom (rate) defined as the number and percentage of subjects who achieved seizure freedom for 24 consecutive weeks during the Treatment Period at any time
Time Frame From Week 2 to Week 50 (During Treatment Period )
Hide Outcome Measure Data
Hide Analysis Population Description

The Full Analysis Set (FAS) consisted of all subjects who received at least 1 (partial) dose of study mediaction and returned at least 1 post-Baseline seizure diary.

A randomized subject was only excluded from the FAS when there was clear evidence that the subject did not take any study medication.

Arm/Group Title Full Analysis Set (LEV Treated Subjects) Full Analysis Set (OXC Treated Subjects)
Hide Arm/Group Description:
250 mg and 500 mg Levetiracetam tablet, 1000 mg-3000 mg/day, maximum 50 weeks including initial up titration of 500 mg/day for 2 weeks
150 mg and 300 mg Oxcarbazepine tablet, 900 mg-2400 mg/day, maximum 50 weeks including 2 weeks of up titration (300 mg/day 1 week then 600 mg/day 1 week)
Overall Number of Participants Analyzed 173 171
Measure Type: Number
Unit of Measure: percentage of subjects
53.8 58.5
4.Secondary Outcome
Title Percentage of Subjects Who Achieved Seizure Freedom During the 48 Weeks Treatment Period
Hide Description 48-week Seizure Freedom (rate) defined as the number and percentage of subjects who achieved seizure freedom during the Treatment Period
Time Frame From Week 2 to Week 50 (During Treatment Period )
Hide Outcome Measure Data
Hide Analysis Population Description

The Full Analysis Set (FAS) consisted of all subjects who received at least 1 (partial) dose of study mediaction and returned at least 1 post-Baseline seizure diary.

A randomized subject was only excluded from the FAS when there was clear evidence that the subject did not take any study medication.

Arm/Group Title Full Analysis Set (LEV Treated Subjects) Full Analysis Set (OXC Treated Subjects)
Hide Arm/Group Description:
250 mg and 500 mg Levetiracetam tablet, 1000 mg-3000 mg/day, maximum 50 weeks including initial up titration of 500 mg/day for 2 weeks
150 mg and 300 mg Oxcarbazepine tablet, 900 mg-2400 mg/day, maximum 50 weeks including 2 weeks of up titration (300 mg/day 1 week then 600 mg/day 1 week)
Overall Number of Participants Analyzed 173 171
Measure Type: Number
Unit of Measure: percentage of subjects
34.7 40.9
Time Frame Adverse Events were collected up to 57 Weeks from Visit 1 (Week -1) to the end of the post-treatment period (down-titration visit, safety follow-up visit).
Adverse Event Reporting Description Adverse Events refer to the Safety Set (SS). SS consisted of all subjects who were randomized and received at least 1 (partial) dose of study medication.
 
Arm/Group Title Levetiracetam Oxcarbazepine
Hide Arm/Group Description

Levetiracetam twice a day treatment Group

250 mg and 500 mg Levetiracetam tablet, 1000 mg-3000 mg/day, maximum 50 weeks including initial up titration of 500 mg/day for 2 weeks

Oxcarbazepine twice a day treatment Group

150 mg and 300 mg Oxcarbazepine tablet, 900 mg-2400 mg/day, maximum 50 weeks including 2 weeks of up titration (300 mg/day 1 week then 600 mg/day 1 week)

All-Cause Mortality
Levetiracetam Oxcarbazepine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Levetiracetam Oxcarbazepine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/173 (8.67%)      15/174 (8.62%)    
Cardiac disorders     
Cardiac arrest * 1  0/173 (0.00%)  0 2/174 (1.15%)  2
Gastrointestinal disorders     
Abdominal pain * 1  1/173 (0.58%)  1 0/174 (0.00%)  0
Diarrhoea * 1  1/173 (0.58%)  1 0/174 (0.00%)  0
Abdominal pain upper * 1  0/173 (0.00%)  0 1/174 (0.57%)  1
General disorders     
Chest discomfort * 1  1/173 (0.58%)  1 0/174 (0.00%)  0
Injury, poisoning and procedural complications     
Fibula fracture * 1  1/173 (0.58%)  1 0/174 (0.00%)  0
Thermal burn * 1  1/173 (0.58%)  1 0/174 (0.00%)  0
Tibia fracture * 1  1/173 (0.58%)  1 0/174 (0.00%)  0
Ankle fracture * 1  0/173 (0.00%)  0 1/174 (0.57%)  1
Comminuted fracture * 1  0/173 (0.00%)  0 1/174 (0.57%)  1
Metabolism and nutrition disorders     
Hyponatraemia * 1  0/173 (0.00%)  0 1/174 (0.57%)  1
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/173 (0.58%)  1 1/174 (0.57%)  1
Flank pain * 1  1/173 (0.58%)  1 0/174 (0.00%)  0
Myalgia * 1  0/173 (0.00%)  0 1/174 (0.57%)  1
Neck pain * 1  0/173 (0.00%)  0 1/174 (0.57%)  1
Nervous system disorders     
Convulsion * 1  4/173 (2.31%)  4 5/174 (2.87%)  5
Dizziness * 1  1/173 (0.58%)  1 0/174 (0.00%)  0
Status epilepticus * 1  1/173 (0.58%)  1 1/174 (0.57%)  1
Encephalopathy * 1  0/173 (0.00%)  0 1/174 (0.57%)  1
Reproductive system and breast disorders     
Endometriosis * 1  1/173 (0.58%)  1 0/174 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Upper airway obstruction * 1  1/173 (0.58%)  1 0/174 (0.00%)  0
Respiratory failure * 1  0/173 (0.00%)  0 1/174 (0.57%)  1
Surgical and medical procedures     
Abortion induced * 1  1/173 (0.58%)  1 1/174 (0.57%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Levetiracetam Oxcarbazepine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   67/173 (38.73%)      93/174 (53.45%)    
Infections and infestations     
Nasopharyngitis * 1  14/173 (8.09%)  15 19/174 (10.92%)  21
Nervous system disorders     
Dizziness * 1  25/173 (14.45%)  30 50/174 (28.74%)  70
Headache * 1  25/173 (14.45%)  29 36/174 (20.69%)  53
Somnolence * 1  22/173 (12.72%)  30 24/174 (13.79%)  30
Skin and subcutaneous tissue disorders     
Rash * 1  3/173 (1.73%)  3 13/174 (7.47%)  16
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA17.0
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB (Study Director)
Organization: UCB Clinical Trial Call Center
Phone: +1 887 822 9493
Layout table for additonal information
Responsible Party: UCB Pharma ( Korea UCB Co., Ltd. )
ClinicalTrials.gov Identifier: NCT01498822     History of Changes
Other Study ID Numbers: N01367
2014-002713-32 ( EudraCT Number )
First Submitted: December 21, 2011
First Posted: December 23, 2011
Results First Submitted: June 25, 2015
Results First Posted: August 20, 2015
Last Update Posted: August 20, 2015