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Trial record 1 of 2 for:    NCT01710657
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A Trial to Evaluate the Efficacy and Safety of Adjunctive Therapy With Lacosamide in Adults 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: NCT01710657
Recruitment Status : Completed
First Posted : October 19, 2012
Results First Posted : February 9, 2015
Last Update Posted : August 25, 2017
Sponsor:
Collaborator:
UCB Japan Co. Ltd.
Information provided by (Responsible Party):
UCB Pharma ( UCB Pharma SA )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Epilepsy
Partial Onset Seizures
Interventions Drug: Lacosamide 50 mg
Drug: Lacosamide 100 mg
Drug: Placebo
Enrollment 548
Recruitment Details A total of 676 subjects with uncontrolled partial-onset seizures (of the 676 subjects, the number of Chinese subjects and Japanese subjects was planned to be 507 and 169, respectively) was planned to be screened and 540 subjects were planned to be enrolled in all regions of Japan and China.
Pre-assignment Details Overall, 692 subjects were screened and 548 subjects were enrolled. The Participant Flow refers to the Safety Set (SS) which was defined as all enrolled subjects who took at least 1 dose of Lacosamide. Reasons for discontinuation were only calculated for the SS. 547 subjects were included in the Safety Set.
Arm/Group Title Placebo Lacosamide 200 mg/Day Lacosamide 400 mg/Day
Hide Arm/Group Description

Matching Placebo for 16 weeks.

Placebo: Matching oral Placebo tablets twice daily for 16 weeks.

Lacosamide Treatment of 200 mg/day (100 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use

Lacosamide Treatment of 400 mg/day (200 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use
Period Title: Overall Study
Started 184 183 180
Titration Period (4 Weeks) 184 183 180
Maintenance Period (12 Weeks) 176 175 168
Completed 166 171 148
Not Completed 18 12 32
Reason Not Completed
Lost to Follow-up             2             0             1
Protocol Violation             2             2             0
Adverse Event             14             8             28
Withdrawal by Subject             0             1             2
Lack of Efficacy             0             1             1
Arm/Group Title Placebo Lacosamide 200 mg/Day Lacosamide 400 mg/Day Total
Hide Arm/Group Description

Matching Placebo for 16 weeks.

Placebo: Matching oral Placebo tablets twice daily for 16 weeks.

Lacosamide Treatment of 200 mg/day (100 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use

Lacosamide Treatment of 400 mg/day (200 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use
Total of all reporting groups
Overall Number of Baseline Participants 184 183 180 547
Hide Baseline Analysis Population Description
The Baseline Characteristics refer to the Safety Set (SS) which was defined as all enrolled subjects who took at least 1 dose of Lacosamide.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 184 participants 183 participants 180 participants 547 participants
<=18 years
20
  10.9%
18
   9.8%
15
   8.3%
53
   9.7%
Between 18 and 65 years
164
  89.1%
163
  89.1%
164
  91.1%
491
  89.8%
>=65 years
0
   0.0%
2
   1.1%
1
   0.6%
3
   0.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 184 participants 183 participants 180 participants 547 participants
31.8  (12.0) 33.2  (12.2) 32.3  (11.9) 32.4  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 184 participants 183 participants 180 participants 547 participants
Female
82
  44.6%
89
  48.6%
76
  42.2%
247
  45.2%
Male
102
  55.4%
94
  51.4%
104
  57.8%
300
  54.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 184 participants 183 participants 180 participants 547 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
184
 100.0%
183
 100.0%
180
 100.0%
547
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 184 participants 183 participants 180 participants 547 participants
Chinese 136 136 133 405
Japanese 48 47 47 142
1.Primary Outcome
Title Change in Partial-Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period
Hide Description

Partial-onset seizure (POS) frequency per 28 days was calculated as:

POS frequency = (Number of POS over the specified time interval) / (Number of days in the interval with available diary data) x 28.

A negative value in Change in Partial-onset seizure frequency indicates a reduction of Partial-onset seizure frequency from Baseline to the Maintenance Period.

Time Frame 8-week Baseline Period (Visit 1 to 3) and 12-week Maintenance Period (Visit 5 to 8)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consists of all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline efficacy assessment.
Arm/Group Title Placebo Lacosamide 200 mg/Day Lacosamide 400 mg/Day
Hide Arm/Group Description:

Matching Placebo for 16 weeks.

Placebo: Matching oral Placebo tablets twice daily for 16 weeks.

Lacosamide Treatment of 200 mg/day (100 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use

Lacosamide Treatment of 400 mg/day (200 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use
Overall Number of Participants Analyzed 183 182 179
Median (Full Range)
Unit of Measure: Seizures per 28 days
-1.22
(-93.0 to 39.8)
-3.33
(-754.3 to 165.2)
-4.50
(-97.5 to 28.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lacosamide 400 mg/Day
Comments

To avoid inflation of Type I error, hypothesis testing followed predefined hierarchical procedure starting LCM 400 mg/day treatment group versus the placebo group.

If the test was not statistically significant, the procedure stopped and no Groups were declared different from placebo. If the test was statistically significant, the treatment group was considered different from placebo and the procedure continued with the LCM 200 mg/day treatment group.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Significant at the 0.05 level. This testing procedure is considered a closed testing procedure and no adjustment of the significance level was necessary.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter % Reduction over Placebo
Estimated Value 39.6
Confidence Interval (2-Sided) 95%
30.5 to 47.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lacosamide 200 mg/Day
Comments

To avoid inflation of Type I error, hypothesis testing followed predefined hierarchical procedure starting LCM 400 mg/day treatment group versus the placebo group.

If the test was not statistically significant, the procedure stopped and no Groups were declared different from placebo. If the test was statistically significant, the treatment group was considered different from placebo and the procedure continued with the LCM 200 mg/day treatment group.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments Significant at the 0.05 level. This testing procedure is considered a closed testing procedure and no adjustment of the significance level was necessary.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter % Reduction over Placebo
Estimated Value 29.4
Confidence Interval (2-Sided) 95%
18.7 to 38.7
Estimation Comments [Not Specified]
2.Secondary Outcome
Title The Proportion of Individual Patients Who Experience a 50 % or Greater Reduction in Seizure Frequency From Baseline to the Maintenance Period (50 % Responder Rate)
Hide Description [Not Specified]
Time Frame 8-week Baseline Period (Visit 1 to 3) to the 12-week Maintenance Period (Visit 5 to 8)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consists of all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline efficacy assessment.
Arm/Group Title Placebo Lacosamide 200 mg/Day Lacosamide 400 mg/Day
Hide Arm/Group Description:

Matching Placebo for 16 weeks.

Placebo: Matching oral Placebo tablets twice daily for 16 weeks.

Lacosamide Treatment of 200 mg/day (100 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use

Lacosamide Treatment of 400 mg/day (200 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use
Overall Number of Participants Analyzed 183 182 179
Measure Type: Number
Unit of Measure: participants
36 70 88
3.Secondary Outcome
Title Percent Change in Partial-Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period
Hide Description Calculates as 28-day seizure frequency during the Maintenance Period - 28-day seizure frequency during the Baseline Period, divided by the 28-day seizure frequency during the Baseline Period with this quantity multiplied by 100. A negative value in percent change from Baseline indicates a decrease in Partial-Onset Seizure frequency from Baseline to the Maintenance Period.
Time Frame 8-week Baseline Period (Visit 1 to 3) to the 12-week Maintenance Period (Visit 5 to 8)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consists of all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline efficacy assessment.
Arm/Group Title Placebo Lacosamide 200 mg/Day Lacosamide 400 mg/Day
Hide Arm/Group Description:

Matching Placebo for 16 weeks.

Placebo: Matching oral Placebo tablets twice daily for 16 weeks.

Lacosamide Treatment of 200 mg/day (100 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use

Lacosamide Treatment of 400 mg/day (200 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use
Overall Number of Participants Analyzed 183 182 179
Median (Full Range)
Unit of Measure: percentage change
-10.10
(-97.6 to 233.5)
-36.75
(-100.0 to 185.5)
-48.78
(-100.0 to 346.4)
4.Secondary Outcome
Title Change in Partial-Onset Seizure Frequency Per 28 Days From Baseline to the Treatment Period (i.e., Titration + Maintenance Period)
Hide Description

Partial-onset seizure (POS) frequency per 28 days was calculated as:

POS frequency = (Number of POS over the specified time interval) / (Number of days in the interval with available diary data) x 28.

A negative value in Change in Partial-onset seizure frequency indicates a reduction of Partial-onset seizure frequency from Baseline to the Treatment Period.

Time Frame 8-week Baseline Period (Visit 1 to 3) to the 16-week Treatment Period (Visit 3 to 8)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consists of all subjects who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline efficacy assessment.
Arm/Group Title Placebo Lacosamide 200 mg/Day Lacosamide 400 mg/Day
Hide Arm/Group Description:

Matching Placebo for 16 weeks.

Placebo: Matching oral Placebo tablets twice daily for 16 weeks.

Lacosamide Treatment of 200 mg/day (100 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use

Lacosamide Treatment of 400 mg/day (200 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use
Overall Number of Participants Analyzed 183 182 179
Median (Full Range)
Unit of Measure: Seizures per 28 days
-1.10
(-102.4 to 102.5)
-3.39
(-670.0 to 138.9)
-4.00
(-92.4 to 34.2)
Time Frame Adverse Events (AEs) were collected from Baseline to the end of the study (up to Week 19).
Adverse Event Reporting Description Treatment Emergent Adverse Events (TEAEs) refer to the Safety Set (SS). The SS includes all randomized subjects who took at least 1 dose of study drug.
 
Arm/Group Title Placebo Lacosamide 200 mg/Day Lacosamide 400 mg/Day
Hide Arm/Group Description

Matching Placebo for 16 weeks.

Placebo: Matching oral Placebo tablets twice daily for 16 weeks.

Lacosamide Treatment of 200 mg/day (100 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use

Lacosamide Treatment of 400 mg/day (200 mg bid) for 16 weeks.

Lacosamide 50 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use

Lacosamide 100 mg: - Active Substance: Lacosamide

  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 100 mg
  • Route of Administration: Oral use
All-Cause Mortality
Placebo Lacosamide 200 mg/Day Lacosamide 400 mg/Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Placebo Lacosamide 200 mg/Day Lacosamide 400 mg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/184 (2.17%)      2/183 (1.09%)      9/180 (5.00%)    
Ear and labyrinth disorders       
Vertigo * 1  1/184 (0.54%)  1 0/183 (0.00%)  0 0/180 (0.00%)  0
Gastrointestinal disorders       
Upper gastrointestinal haemorrhage * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
Hepatobiliary disorders       
Drug-induced liver injury * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
Infections and infestations       
Bronchitis * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
Pneumonia * 1  1/184 (0.54%)  1 0/183 (0.00%)  0 1/180 (0.56%)  1
Injury, poisoning and procedural complications       
Comminuted fracture * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
Hand fracture * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
Subdural haematoma * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
Metabolism and nutrition disorders       
Diabetes mellitus * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer * 1  0/184 (0.00%)  0 1/183 (0.55%)  1 0/180 (0.00%)  0
Nervous system disorders       
Dizziness * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
Grand mal convulsion * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
Status epilepticus * 1  2/184 (1.09%)  2 0/183 (0.00%)  0 0/180 (0.00%)  0
Psychiatric disorders       
Epileptic psychosis * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
Suicide attempt * 1  0/184 (0.00%)  0 1/183 (0.55%)  1 0/180 (0.00%)  0
Surgical and medical procedures       
Abortion induced * 1  0/184 (0.00%)  0 0/183 (0.00%)  0 1/180 (0.56%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Lacosamide 200 mg/Day Lacosamide 400 mg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   77/184 (41.85%)      87/183 (47.54%)      112/180 (62.22%)    
Eye disorders       
Diplopia * 1  4/184 (2.17%)  5 4/183 (2.19%)  8 13/180 (7.22%)  15
Gastrointestinal disorders       
Vomiting * 1  4/184 (2.17%)  4 5/183 (2.73%)  6 14/180 (7.78%)  18
Nausea * 1  9/184 (4.89%)  10 7/183 (3.83%)  8 10/180 (5.56%)  11
Infections and infestations       
Nasopharyngitis * 1  24/184 (13.04%)  41 28/183 (15.30%)  40 29/180 (16.11%)  36
Upper respiratory tract infection * 1  22/184 (11.96%)  31 10/183 (5.46%)  14 19/180 (10.56%)  28
Investigations       
White blood cell count decreased * 1  2/184 (1.09%)  2 8/183 (4.37%)  14 10/180 (5.56%)  12
Nervous system disorders       
Dizziness * 1  24/184 (13.04%)  32 33/183 (18.03%)  57 63/180 (35.00%)  118
Somnolence * 1  9/184 (4.89%)  10 18/183 (9.84%)  26 19/180 (10.56%)  21
Headache * 1  11/184 (5.98%)  21 16/183 (8.74%)  18 19/180 (10.56%)  32
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
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 Clinical Trial Call Center
Organization: UCB
Phone: +1 877 822 9493 (UCB)
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB Pharma SA )
ClinicalTrials.gov Identifier: NCT01710657    
Other Study ID Numbers: EP0008
2014-003622-41 ( EudraCT Number )
JapicCTI-121988 ( Registry Identifier: JAPIC )
First Submitted: October 17, 2012
First Posted: October 19, 2012
Results First Submitted: January 22, 2015
Results First Posted: February 9, 2015
Last Update Posted: August 25, 2017