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Study of Lacosamide as an Adjunctive Drug Treatment for Epilepsy in Patients With Brain Tumors (VIBES)

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ClinicalTrials.gov Identifier: NCT02276053
Recruitment Status : Completed
First Posted : October 27, 2014
Results First Posted : August 19, 2019
Last Update Posted : June 1, 2020
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES GmbH )

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Brain Tumor Related Epilepsy (BTRE)
Enrollment 93
Recruitment Details The study started to enroll patients in November 2014 and concluded in December 2017.
Pre-assignment Details The Participant Flow refers to the Safety Set (SS), which was defined as all patients included in the study receiving treatment with LCM at least once in the study.
Arm/Group Title Lacosamide
Hide Arm/Group Description Patients with brain tumor-related epilepsy (BTRE), secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of lacosamide (LCM) treatment, routinely treated with lacosamide as add on to one or two baseline anti-epileptic drugs (AEDs) and who were included in the Safety Set (SS).
Period Title: Overall Study
Started 93
Completed 79
Not Completed 14
Reason Not Completed
Death             2
Adverse Event             5
Lack of Efficacy             2
Withdrawal by Subject             1
Patient does not meet selection criteria             3
Patient needs to increase baseline AED             1
Arm/Group Title Lacosamide
Hide Arm/Group Description Patients with brain tumor-related epilepsy (BTRE), secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of lacosamide (LCM) treatment, routinely treated with lacosamide as add on to one or two baseline anti-epileptic drugs (AEDs) and who were included in the Safety Set (SS).
Overall Number of Baseline Participants 93
Hide Baseline Analysis Population Description
The Baseline Characteristics refer to the Safety Set (SS), which was defined as all patients included in the study receiving treatment with LCM at least once in the study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 93 participants
<=18 years
1
   1.1%
Between 18 and 65 years
82
  88.2%
>=65 years
10
  10.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 93 participants
44.5  (14.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 93 participants
Female
43
  46.2%
Male
50
  53.8%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
1.Primary Outcome
Title Percentage of Patients With Response at the End of the 6-month Observation Period
Hide Description A responder is a patient experiencing a 50 % or greater reduction in partial onset seizure frequency from Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period)
Time Frame Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Full Analysis Set (FAS), which included all patients in the Safety Set (SS) who had at least 1 post Baseline Patient Global Impression of Change (PGIC) or seizure assessment.
Arm/Group Title Lacosamide (FAS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the Full Analysis Set (FAS), having at least one post-Baseline Patient Global Impression of Change or seizure assessment.
Overall Number of Participants Analyzed 86
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
76.7
(66.4 to 85.2)
2.Primary Outcome
Title Patient Global Impression of Change (PGIC) Rating at Visit 3
Hide Description

The Patient Global Impression of Change scale is a seven-point scale for patients to rate their general health status at the end of the study compared to how they felt before entering the study. Scores 1 to 3 mean improvement, score 4 means no change, and scores 5 to 7 mean worsening.

The category 'Improved' represents the sum of Very Much Improved, Much Improved, and Minimally Improved.

The category 'Worsened' represents the sum of Minimally Worse, Much Worse, and Very Much Worse.

Time Frame Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Full Analysis Set (FAS), which included all patients in the Safety Set (SS) who had at least 1 post Baseline Patient Global Impression of Change (PGIC) or seizure assessment.
Arm/Group Title Lacosamide (FAS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the Full Analysis Set (FAS), having at least one post-Baseline Patient Global Impression of Change or seizure assessment.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Improved
49
  64.5%
No change
17
  22.4%
Worsened
10
  13.2%
3.Secondary Outcome
Title Percentage of Patients With Retention on Lacosamide (LCM) at the End of the 6-month Observation Period
Hide Description The retention rate was defined as the percentage of patients remaining in the study and on Lacosamide treatment for 6 months (6 month retention rate).
Time Frame Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Safety Set (SS), which included all patients who received treatment with lacosamide (LCM) at least once in the study.
Arm/Group Title Lacosamide (SS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the SS.
Overall Number of Participants Analyzed 93
Measure Type: Number
Unit of Measure: percentage of patients
63.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lacosamide (SS)
Comments The retention rate was derived using Kaplan-Meier methodology where patients who completed the study were censored at the date of last administration of LCM in the study.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Retention rate
Estimated Value 86.0
Confidence Interval (2-Sided) 95%
79.0 to 93.1
Estimation Comments

Confidence intervals for the 6-month retention rate were calculated using Greenwood's formula.

Addition of a note: Not all patients had an Observation Period of 6 months.

4.Secondary Outcome
Title Time to Discontinuation of Lacosamide (LCM) Treatment From the Date of First Dose of LCM
Hide Description Time between first dose of LCM to discontinuation of LCM treatment was measured in days.
Time Frame From first dose to discontinuation, over a 6-month Observation Period
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Safety Set (SS), which included all patients who received treatment with lacosamide (LCM) at least once in the study.
Arm/Group Title Lacosamide (SS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the SS.
Overall Number of Participants Analyzed 93
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
[1]
Due to low number of participants with events, Kaplan-Meier estimation of percentage of event-free subjects was high and corresponding standard error was small, preventing estimation of median time to event and 95% confidence interval boundaries.
5.Secondary Outcome
Title Change From Visit 1 (Baseline) to Visit 3 (Month 6 or End of Observation Period) in the 5 Level EuroQol-5 Dimension Quality of Life Assessment (EQ-5D-5L) Visual Analogue Scale (VAS) Score
Hide Description EQ-5D-5L: 5 Level EuroQol-5 Dimension Quality of Life Assessment is a patient-completed questionnaire for patients to rate their quality of life status in five questions and a 0 (no pain) - 100 (worst pain) score vertical visual analogue scale. The Change from Baseline is calculated for this endpoint, negative values indicate improvement and positive values indicate worsening.
Time Frame Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Full Analysis Set (FAS), which included all patients in the Safety Set (SS) who had at least 1 post Baseline Patient Global Impression of Change (PGIC) or seizure assessment.
Arm/Group Title Lacosamide (FAS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the Full Analysis Set (FAS), having at least one post-Baseline Patient Global Impression of Change or seizure assessment.
Overall Number of Participants Analyzed 72
Mean (Standard Deviation)
Unit of Measure: scores on a scale
1.3  (16.4)
6.Secondary Outcome
Title Change From Visit 1 (Baseline) to Visit 3 (Month 6 or End of Observation Period) in the 5 Level EuroQol-5 Dimension Quality of Life Assessment (EQ-5D-5L) Change in Utility as Converted From the 5 Dimensions
Hide Description EQ-5D-5L: 5 Level EuroQol-5 descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression with five response levels for each dimension: no problems, slight problems, moderate problems, severe problems and extreme problems. This 5-dimension health status is converted into a numerical utility value using the UK value set, as per EuroQOL guidelines. The utility score ranges from 0 to 1 (0=worst imaginable health state, 1=best imaginable health state). The Change from Baseline is calculated for this endpoint, negative values indicate worsening and positive values indicate improvement.
Time Frame Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Full Analysis Set (FAS), which included all patients in the Safety Set (SS) who had at least 1 post Baseline Patient Global Impression of Change (PGIC) or seizure assessment.
Arm/Group Title Lacosamide (FAS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the Full Analysis Set (FAS), having at least one post-Baseline Patient Global Impression of Change or seizure assessment.
Overall Number of Participants Analyzed 73
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-0.01  (0.20)
7.Secondary Outcome
Title Change From Visit 1 (Baseline) to Visit 3 (Month 6 or End of Observation Period) in the M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Hide Description MDASI-BT is a 2-part patient completed questionnaire where patients have to answer 22 questions about their brain tumor-related symptoms and 6 questions about how these symptoms interfere with their life. The mean core symptom severity is derived as the mean of the 13 core symptom items, the mean module symptom severity is derived as the mean of the 9 brain tumor specific symptom items and the mean total symptom severity is derived as the mean of all 22 symptom items. The mean interference is derived as the mean of the 6 interference items. For each score, at least 50% of the items needs to be answered for the score to be calculated. Mean core, mean module and mean total symptom severity scores are ranging from 0 to 10 (0=not present 10=as bad as you can imagine). Mean interference score is ranging from 0 to 10 (0= did not interfere 10= interfered completely). The Change from Baseline is calculated, negative values indicate improvement, positive values indicate worsening.
Time Frame Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Full Analysis Set (FAS), which included all patients in the Safety Set (SS) who had at least 1 post Baseline Patient Global Impression of Change (PGIC) or seizure assessment.
Arm/Group Title Lacosamide (FAS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the Full Analysis Set (FAS), having at least one post-Baseline Patient Global Impression of Change or seizure assessment.
Overall Number of Participants Analyzed 73
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Mean core symptom severity Number Analyzed 73 participants
0.1  (1.3)
Mean module symptom severity Number Analyzed 70 participants
-0.1  (1.6)
Mean total severity Number Analyzed 73 participants
0.0  (1.2)
Mean interference Number Analyzed 70 participants
-0.5  (2.4)
8.Secondary Outcome
Title Actual Change From Visit 1 (Baseline) to Visit 3 (Month 6 or End of Observation Period) in Seizure Frequency (Seizures Per 28 Days)
Hide Description

The actual change in seizure frequency from Baseline to Month 6 is calculated as the seizure frequency at Month 6 minus the seizure frequence at Baseline.

The seizure frequency at each time point is calculated as number of seizures per 28 days.

Time Frame Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Full Analysis Set (FAS), which included all patients in the Safety Set (SS) who had at least 1 post Baseline Patient Global Impression of Change (PGIC) or seizure assessment.
Arm/Group Title Lacosamide (FAS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the Full Analysis Set (FAS), having at least one post-Baseline Patient Global Impression of Change or seizure assessment.
Overall Number of Participants Analyzed 78
Median (Inter-Quartile Range)
Unit of Measure: seizures per 28 days
-2.9
(-9.1 to -0.9)
9.Secondary Outcome
Title Percentage Change From Baseline in Seizure Frequency
Hide Description The percentage change from Baseline to Month 6 in seizure frequency is the actual change in seizure frequency for this period compared to the Baseline seizure frequency, which is considered 100 %.
Time Frame Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Full Analysis Set (FAS), which included all patients in the Safety Set (SS) who had at least 1 post Baseline Patient Global Impression of Change (PGIC) or seizure assessment.
Arm/Group Title Lacosamide (FAS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the Full Analysis Set (FAS), having at least one post-Baseline Patient Global Impression of Change or seizure assessment.
Overall Number of Participants Analyzed 78
Median (Inter-Quartile Range)
Unit of Measure: percent change
-85.2
(-100.0 to -55.5)
10.Secondary Outcome
Title Percentage of Patients With Seizure-free Status (Yes/No) at the End of the 6-month Observational Period
Hide Description Percentage of patients achieving a seizure-free status at the end of the 6-month Observation Period.
Time Frame Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Full Analysis Set (FAS), which included all patients in the Safety Set (SS) who had at least 1 post Baseline Patient Global Impression of Change (PGIC) or seizure assessment.
Arm/Group Title Lacosamide (FAS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the Full Analysis Set (FAS), having at least one post-Baseline Patient Global Impression of Change or seizure assessment.
Overall Number of Participants Analyzed 86
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
34.9
(24.9 to 45.9)
11.Secondary Outcome
Title Discontinuation Rate of Lacosamide (LCM) Due to Adverse Drug Reactions (ADRs)
Hide Description Discontinuation rate due to ADRs is the number of patients that discontinued from the study and from LCM treatment due to ADRs during the 6 months of observation.
Time Frame Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Safety Set (SS), which included all patients who received treatment with lacosamide (LCM) at least once in the study.
Arm/Group Title Lacosamide (SS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the SS.
Overall Number of Participants Analyzed 93
Measure Type: Count of Participants
Unit of Measure: Participants
5
   5.4%
12.Secondary Outcome
Title Discontinuation Rate of Lacosamide (LCM) Due to Lack of Effectiveness
Hide Description Discontinuation rate due to lack of effectiveness is the number of patients that discontinued from the study and from LCM treatment due to lack of effectiveness during the 6 months of observation.
Time Frame Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Safety Set (SS), which included all patients who received treatment with lacosamide (LCM) at least once in the study.
Arm/Group Title Lacosamide (SS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the SS.
Overall Number of Participants Analyzed 93
Measure Type: Count of Participants
Unit of Measure: Participants
7
   7.5%
13.Secondary Outcome
Title Clinical Global Impression of Change (CGIC) Rating at Visit 3 (Month 6 or End of Observation Period)
Hide Description

The Clinical Global Impression of Change is a seven-point scale for the treating physician to rate the patient's general health status at the end of the study compared to how the patient felt before entering the study. Scores 1 to 3 mean improvement, score 4 means no change, and scores 5 to 7 mean worsening.

The category 'Improved' represents the sum of Very Much Improved, Much Improved, and Minimally Improved.

The category 'Worsened' represents the sum of Minimally Worse, Much Worse, and Very Much Worse.

Time Frame Visit 3 (Month 6 or end of Observation Period)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Full Analysis Set (FAS), which included all patients in the Safety Set (SS) who had at least 1 post Baseline Patient Global Impression of Change (PGIC) or seizure assessment.
Arm/Group Title Lacosamide (FAS)
Hide Arm/Group Description:
Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the Full Analysis Set (FAS), having at least one post-Baseline Patient Global Impression of Change or seizure assessment.
Overall Number of Participants Analyzed 81
Measure Type: Count of Participants
Unit of Measure: Participants
Impoved
52
  64.2%
No change
19
  23.5%
Worsened
10
  12.3%
Time Frame From Baseline and up to month 6
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lacosamide (SS)
Hide Arm/Group Description Patients with BTRE, secondary to low-grade glioma (WHO Grade 1 to 2) and with at least 1 partial-onset seizure in the 8 weeks prior to start of LCM treatment, routinely treated with lacosamide as add on to one or two baseline AEDs and who were included in the SS.
All-Cause Mortality
Lacosamide (SS)
Affected / at Risk (%)
Total   2/93 (2.15%)    
Hide Serious Adverse Events
Lacosamide (SS)
Affected / at Risk (%) # Events
Total   5/93 (5.38%)    
Hepatobiliary disorders   
Cholestasis * 1  1/93 (1.08%)  1
Investigations   
Blood alkaline phosphatase increased * 1  1/93 (1.08%)  1
Gamma-glutamyltransferase increased * 1  1/93 (1.08%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Brain neoplasm * 1  1/93 (1.08%)  1
Nervous system disorders   
Brain oedema * 1  1/93 (1.08%)  1
Coma * 1  1/93 (1.08%)  1
Headache * 1  1/93 (1.08%)  1
Partial seizures * 1  1/93 (1.08%)  1
Status epilepticus * 1  1/93 (1.08%)  1
Syncope * 1  1/93 (1.08%)  1
1
Term from vocabulary, 20.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lacosamide (SS)
Affected / at Risk (%) # Events
Total   9/93 (9.68%)    
Ear and labyrinth disorders   
Vertigo * 1  5/93 (5.38%)  5
Nervous system disorders   
Headache * 1  5/93 (5.38%)  5
1
Term from vocabulary, 20.1
*
Indicates events were collected by non-systematic assessment
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
Organization: Cares
Phone: +1844 599 ext 2273
EMail: UCBCares@ucb.com
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier: NCT02276053    
Other Study ID Numbers: EP0045
First Submitted: October 23, 2014
First Posted: October 27, 2014
Results First Submitted: December 4, 2018
Results First Posted: August 19, 2019
Last Update Posted: June 1, 2020