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Trial record 1 of 1 for:    NCT01954121
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Open-label, Randomized, Active-controlled Study of LEV Used as Monotherapy in Patients With Partial-Onset Seizures

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: NCT01954121
Recruitment Status : Completed
First Posted : October 1, 2013
Results First Posted : August 11, 2016
Last Update Posted : August 15, 2017
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Pharma SA )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Epilepsy
Partial Seizures
Interventions Drug: Levetiracetam
Drug: Carbamazepine
Enrollment 436
Recruitment Details This study started to enroll subjects in China in September 2013.
Pre-assignment Details Participant Flow refers to the Randomized Set which consists of all subjects who were randomized in this study.
Arm/Group Title Levetiracetam Carbamazepine-IR
Hide Arm/Group Description During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Levetiracetam (LEV) 250 mg bid. During Stabilization and Evaluation Period (27 weeks) LEV was taken bid 500 mg. During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Carbamazepine immediate-release (CBZ-IR) 200 mg qd. During Stabilization and Evaluation (27 weeks) Period CBZ-IR was taken bid 200 mg.
Period Title: Overall Study
Started 220 216
Completed 93 125
Not Completed 127 91
Reason Not Completed
Lack of Efficacy             94             41
Protocol Violation             0             2
Lost to Follow-up             5             6
Withdrawal by Subject             18             12
Pregnancy             1             1
AE, serious fatal             1             0
AE, non-serious non-fatal             5             22
SAE, non-fatal             1             4
Non-compliant with study procedures             1             0
Non-compliant patient             1             1
Subject did not follow instructions             0             2
Arm/Group Title Levetiracetam (Safety Set) Carbamazepine-IR (Safety Set) Total Title
Hide Arm/Group Description During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Levetiracetam (LEV) 250 mg bid. During Stabilization and Evaluation Period (27 weeks) LEV was taken bid 500 mg. During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Carbamazepine immediate-release (CBZ-IR) 200 mg qd. During Stabilization and Evaluation (27 weeks) Period CBZ-IR was taken bid 200 mg. [Not Specified]
Overall Number of Baseline Participants 218 215 433
Hide Baseline Analysis Population Description
The Baseline Characteristics refers to the Safety Set (SS) which consists of all subjects who were randomized and received at least 1 dose of trial medication.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 218 participants 215 participants 433 participants
<=18 years
20
   9.2%
22
  10.2%
42
   9.7%
Between 18 and 65 years
184
  84.4%
186
  86.5%
370
  85.5%
>=65 years
14
   6.4%
7
   3.3%
21
   4.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
mean (standard deviation) Number Analyzed 218 participants 215 participants 433 participants
37.8  (16.2) 33.3  (14.3) 35.6  (15.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 218 participants 215 participants 433 participants
Female
106
  48.6%
94
  43.7%
200
  46.2%
Male
112
  51.4%
121
  56.3%
233
  53.8%
1.Primary Outcome
Title Proportion of Subjects Remaining Seizure Free During the 6-months Evaluation Period
Hide Description [Not Specified]
Time Frame 6-months Evaluation Period (From Week 4 to Week 30)
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Set consisted of all subjects in the Full Analysis Set who entered the Evaluation Period and who did not have any important protocol deviations determined to impact the interpretation of efficacy. Criteria that might impact the assessment of efficacy was determined during a Data Review Meeting before the database lock.
Arm/Group Title Levetiracetam (Per Protocol Set) Carbamazepine-IR (Per Protocol Set)
Hide Arm/Group Description:
During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Levetiracetam (LEV) 250 mg bid. During Stabilization and Evaluation Period (27 weeks) LEV was taken bid 500 mg.
During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Carbamazepine immediate-release (CBZ-IR) 200 mg qd. During Stabilization and Evaluation (27 weeks) Period CBZ-IR was taken bid 200 mg.
Overall Number of Participants Analyzed 186 171
Measure Type: Number
Unit of Measure: percentage of subjects
47.3 68.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levetiracetam (Per Protocol Set), Carbamazepine-IR (Per Protocol Set)
Comments The adjusted absolute difference in treatment group seizure-free proportions (referenced as 'Adjusted difference in proportions' in 'Method of Estimation' below) was derived from the adjusted treatment group proportions of seizure-free subjects. The adjusted proportions were derived from a logistic regression model of seizure freedom using treatment and the categories for the number of seizures in the 3-month period prior to Visit 1 (≤2 seizures and >2 seizures) as covariates.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority margin for the adjusted difference in seizure free proportion in the LEV minus the seizure free proportion in the CBZ-IR group was set to absolute -20% points.
Method of Estimation Estimation Parameter adjusted difference in proportions
Estimated Value -22.9
Confidence Interval (2-Sided) 95%
-33.1 to -12.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Proportion of Subjects Retained in the Study for the Duration of the Period Covering the Up Titration Period, Stabilization Period, and Evaluation Period
Hide Description [Not Specified]
Time Frame From Week 1 to Week 30
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Set consisted of all subjects in the Full Analysis Set who entered the Evaluation Period and who did not have any important protocol deviations determined to impact the interpretation of efficacy. Criteria that might impact the assessment of efficacy was determined during a Data Review Meeting before the database lock.
Arm/Group Title Levetiracetam (Per Protocol Set) Carbamazepine-IR (Per Protocol Set)
Hide Arm/Group Description:
During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Levetiracetam (LEV) 250 mg bid. During Stabilization and Evaluation Period (27 weeks) LEV was taken bid 500 mg.
During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Carbamazepine immediate-release (CBZ-IR) 200 mg qd. During Stabilization and Evaluation (27 weeks) Period CBZ-IR was taken bid 200 mg.
Overall Number of Participants Analyzed 186 171
Measure Type: Number
Unit of Measure: percentage of subjects
48.4 70.2
3.Secondary Outcome
Title Time to First Seizure or Discontinuation Due to an Adverse Event (AE) / Lack of Efficacy (LOE) During the Evaluation Period
Hide Description Number of qualifying events is reported because it is the only descriptive measure available from the proportional hazards model, that was applied.
Time Frame From first day in the Evaluation Period (Week 4) up to end of the Evaluation Period (Week 30)
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Set consisted of all subjects in the Full Analysis Set who entered the Evaluation Period and who did not have any important protocol deviations determined to impact the interpretation of efficacy. Criteria that might impact the assessment of efficacy was determined during a Data Review Meeting before the database lock.
Arm/Group Title Levetiracetam (Per Protocol Set) Carbamazepine-IR (Per Protocol Set)
Hide Arm/Group Description:
During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Levetiracetam (LEV) 250 mg bid. During Stabilization and Evaluation Period (27 weeks) LEV was taken bid 500 mg.
During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Carbamazepine immediate-release (CBZ-IR) 200 mg qd. During Stabilization and Evaluation (27 weeks) Period CBZ-IR was taken bid 200 mg.
Overall Number of Participants Analyzed 186 171
Measure Type: Number
Unit of Measure: events
88 45
4.Secondary Outcome
Title Time to First Seizure During the Evaluation Period
Hide Description Number of qualifying events is reported because it is the only descriptive measure available from the proportional hazards model, that was applied.
Time Frame From first day in the Evaluation Period (Week 4) up to end of the Evaluation Period (Week 30)
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Set consisted of all subjects in the Full Analysis Set who entered the Evaluation Period and who did not have any important protocol deviations determined to impact the interpretation of efficacy. Criteria that might impact the assessment of efficacy was determined during a Data Review Meeting before the database lock.
Arm/Group Title Levetiracetam (Per Protocol Set) Carbamazepine-IR (Per Protocol Set)
Hide Arm/Group Description:
During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Levetiracetam (LEV) 250 mg bid. During Stabilization and Evaluation Period (27 weeks) LEV was taken bid 500 mg.
During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Carbamazepine immediate-release (CBZ-IR) 200 mg qd. During Stabilization and Evaluation (27 weeks) Period CBZ-IR was taken bid 200 mg.
Overall Number of Participants Analyzed 186 171
Measure Type: Number
Unit of Measure: events
87 39
5.Secondary Outcome
Title Time to First Seizure During the Period Covering the Up Titration Period, Stabilization Period, and Evaluation Period From the First Dose of Study Drug
Hide Description Number of qualifying events is reported because it is the only descriptive measure available from the proportional hazards model, that was applied.
Time Frame From Randomization (Week 1) up to Evaluation Visit (Week 30)
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Set consisted of all subjects in the Full Analysis Set who entered the Evaluation Period and who did not have any important protocol deviations determined to impact the interpretation of efficacy. Criteria that might impact the assessment of efficacy was determined during a Data Review Meeting before the database lock.
Arm/Group Title Levetiracetam (Per Protocol Set) Carbamazepine-IR (Per Protocol Set)
Hide Arm/Group Description:
During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Levetiracetam (LEV) 250 mg bid. During Stabilization and Evaluation Period (27 weeks) LEV was taken bid 500 mg.
During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Carbamazepine immediate-release (CBZ-IR) 200 mg qd. During Stabilization and Evaluation (27 weeks) Period CBZ-IR was taken bid 200 mg.
Overall Number of Participants Analyzed 186 171
Measure Type: Number
Unit of Measure: events
97 57
Time Frame Adverse Events (AEs) were collected from Visit 1 (Week 0) until Safety Follow Up Visit (Week 35).
Adverse Event Reporting Description Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Levetiracetam or Carbamezepine immediate-release.
 
Arm/Group Title Levetiracetam (Safety Set) Carbamazepine-IR (Safety Set)
Hide Arm/Group Description During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Levetiracetam (LEV) 250 mg bid. During Stabilization and Evaluation Period (27 weeks) LEV was taken bid 500 mg. During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Carbamazepine immediate-release (CBZ-IR) 200 mg qd. During Stabilization and Evaluation (27 weeks) Period CBZ-IR was taken bid 200 mg.
All-Cause Mortality
Levetiracetam (Safety Set) Carbamazepine-IR (Safety Set)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Levetiracetam (Safety Set) Carbamazepine-IR (Safety Set)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/218 (4.13%)      11/215 (5.12%)    
Blood and lymphatic system disorders     
Thrombocytopenic purpura * 1  0/218 (0.00%)  0 1/215 (0.47%)  1
General disorders     
Peripheral swelling * 1  0/218 (0.00%)  0 1/215 (0.47%)  1
Infections and infestations     
Lung infection * 1  0/218 (0.00%)  0 1/215 (0.47%)  1
Injury, poisoning and procedural complications     
Brain contusion * 1  1/218 (0.46%)  1 0/215 (0.00%)  0
Burns third degree * 1  1/218 (0.46%)  1 0/215 (0.00%)  0
Epidural haemorrhage * 1  1/218 (0.46%)  1 0/215 (0.00%)  0
Hand fracture * 1  1/218 (0.46%)  1 1/215 (0.47%)  1
Overdose * 1  0/218 (0.00%)  0 1/215 (0.47%)  1
Patella fracture * 1  0/218 (0.00%)  0 1/215 (0.47%)  1
Rib Fracture * 1  0/218 (0.00%)  0 1/215 (0.47%)  1
Musculoskeletal and connective tissue disorders     
Spinal osteoarthritis * 1  1/218 (0.46%)  1 0/215 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer * 1  0/218 (0.00%)  0 1/215 (0.47%)  1
Nervous system disorders     
Status epilepticus * 1  2/218 (0.92%)  2 1/215 (0.47%)  1
Epilepsy * 1  1/218 (0.46%)  1 1/215 (0.47%)  1
Seizure * 1  1/218 (0.46%)  1 0/215 (0.00%)  0
Subarachnoid haemorrhage * 1  1/218 (0.46%)  1 0/215 (0.00%)  0
Memory impairment * 1  0/218 (0.00%)  0 1/215 (0.47%)  1
Reproductive system and breast disorders     
Menopausal symptoms * 1  1/218 (0.46%)  1 0/215 (0.00%)  0
Skin and subcutaneous tissue disorders     
Drug eruption * 1  0/218 (0.00%)  0 1/215 (0.47%)  1
Rash * 1  0/218 (0.00%)  0 1/215 (0.47%)  1
Surgical and medical procedures     
Abortion induced * 1  1/218 (0.46%)  1 2/215 (0.93%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA18.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Levetiracetam (Safety Set) Carbamazepine-IR (Safety Set)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   92/218 (42.20%)      93/215 (43.26%)    
Infections and infestations     
Nasopharyngitis * 1  40/218 (18.35%)  48 32/215 (14.88%)  42
Upper respiratory tract infection * 1  12/218 (5.50%)  16 16/215 (7.44%)  18
Urinary tract infection * 1  11/218 (5.05%)  12 5/215 (2.33%)  5
Investigations     
Blood cholesterol increased * 1  6/218 (2.75%)  6 11/215 (5.12%)  11
Gamma-glutamyltransferase increased * 1  2/218 (0.92%)  2 11/215 (5.12%)  11
White blood cell count decreased * 1  1/218 (0.46%)  1 11/215 (5.12%)  14
Nervous system disorders     
Dizziness * 1  33/218 (15.14%)  48 18/215 (8.37%)  29
Somnolence * 1  20/218 (9.17%)  25 7/215 (3.26%)  8
Headache * 1  19/218 (8.72%)  33 16/215 (7.44%)  47
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA18.0
[Not Specified]
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 Cares
Phone: +1 887 822 9493
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB Pharma SA )
ClinicalTrials.gov Identifier: NCT01954121    
Other Study ID Numbers: N01364
First Submitted: September 26, 2013
First Posted: October 1, 2013
Results First Submitted: March 18, 2016
Results First Posted: August 11, 2016
Last Update Posted: August 15, 2017