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Trial record 1 of 2 for:    NCT02408523
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A Study to Assess the Safety and Efficacy of Lacosamide Versus Placebo (a Pill Without Active Medication) in Patients With Idiopathic Generalised Epilepsy Who Are Already Taking Anti-epileptic Medications (VALOR)

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: NCT02408523
Recruitment Status : Completed
First Posted : April 3, 2015
Results First Posted : April 16, 2020
Last Update Posted : May 20, 2020
Sponsor:
Collaborator:
Pharmaceutical Research Associates
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES, Inc. )

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: Lacosamide Tablet
Drug: Lasosamide Oral Solution
Other: Placebo Tablet
Other: Placebo Oral Solution
Enrollment 242
Recruitment Details The study started to enroll patients in April 2015 and concluded in May 2019.
Pre-assignment Details

Completed study was defined as meeting any exit criteria or completing the 24-week Treatment Period with < 2 PGTCS. After Treatment Period participants enrolled either in a 4-week Transition Period (entered EP0012) or up to a 4-week Taper Period and a 30-day Safety Follow-up Period (did not enter EP0012).

Participant Flow refers to the Safety Set.

Arm/Group Title Placebo Lacosamide
Hide Arm/Group Description

Placebo 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400 mg/day for adult and pediatric participants >= 50 kg.

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants < 30 kg).

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400 mg/day for adult and pediatric participants with more or equal than (>=) 50 kilograms (kg).

Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants with less than (<) 30 kg).

Lasosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Period Title: Overall Study
Started 121 121
Completed Treatment Period 110 103
Enrolled Transition Period 108 101
Enrolled Taper Period 7 9
Enrolled Safety Folllow-up Period 10 11
Completed 110 103
Not Completed 11 18
Reason Not Completed
Adverse Event             4             10
Lack of Efficacy             0             1
Protocol Violation             1             2
Lost to Follow-up             2             3
Withdrawal by Subject             3             1
Sponsor request             1             0
Did not satisfy extension conditions             0             1
Arm/Group Title Placebo Lacosamide Total Title
Hide Arm/Group Description

Placebo 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400 mg/day for adult and pediatric participants >= 50 kg.

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants < 30 kg).

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400 mg/day for adult and pediatric participants with more or equal than (>=) 50 kilograms (kg).

Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants with less than (<) 30 kg).

Lasosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

[Not Specified]
Overall Number of Baseline Participants 121 121 242
Hide Baseline Analysis Population Description
Baseline Characteristics refer to the Safety Set (SS) which was a subset of the Randomized Set (RS) and consisted of all study participants who had been treated with at least 1 dose of study medication, either LCM or Placebo.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants 121 participants 242 participants
<=18 years
27
  22.3%
28
  23.1%
55
  22.7%
Between 18 and 65 years
93
  76.9%
92
  76.0%
185
  76.4%
>=65 years
1
   0.8%
1
   0.8%
2
   0.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 121 participants 121 participants 242 participants
27.64  (12.45) 27.82  (13.13) 27.73  (12.77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants 121 participants 242 participants
Female
76
  62.8%
66
  54.5%
142
  58.7%
Male
45
  37.2%
55
  45.5%
100
  41.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants 121 participants 242 participants
American Indian/Alaskan Native
1
   0.8%
1
   0.8%
2
   0.8%
Asian
25
  20.7%
18
  14.9%
43
  17.8%
Black
2
   1.7%
2
   1.7%
4
   1.7%
White
89
  73.6%
97
  80.2%
186
  76.9%
Other/Mixed
4
   3.3%
3
   2.5%
7
   2.9%
1.Primary Outcome
Title Time to the Second Primary Generalized Tonic Clonic (PGTC) Seizure During the 24-week Treatment Period From Visit 2 (Week 0) to Visit 10 (Week 24)
Hide Description

The primary efficacy variable was the time to the second primary generalized tonic clonic seizure (PGTCS) during the 24-week Treatment Period. Relative difference between groups (Lacosamide vs Placebo) was expressed as Hazard Ratio.

The indicated measured values are the observed number of events of second PGTCS in the treatment period which form the basis of the statistical analysis of the time to event analysis.

The hazard ratio compares 2 treatment groups for the times to a specified number of events (125) for the combined treatment groups, and so both the number of events and the times until those events pertain to the computation of the hazard ratio.

A Hazard Ratio below 1 indicates time to second PGTCS was improved for LCM compared to Placebo.

Time Frame During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description

The Full Analysis Set (FAS) was a subset of the Safety Set (SS) that consisted of all study participants with at least 1 seizure diary assessment during the Treatment Period.

1 patient from the Lacosamide (FAS) group was randomized after the 125th event and did not appear in this analysis.

Arm/Group Title Placebo (FAS) Lacosamide (FAS)
Hide Arm/Group Description:

Placebo 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400mg/day for adult and pediatric participants >= 50 kg.

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants < 30 kg).

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the Full Analysis Set (FAS).

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400 mg/day for adult and pediatric participants with more or equal than (>=) 50 kilograms (kg).

Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants with less than (<) 30 kg).

Lasosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the FAS.

Overall Number of Participants Analyzed 121 118
Measure Type: Number
Unit of Measure: events
76 49
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Lacosamide (FAS)
Comments Comparison of LCM versus Placebo was based on a Cox proportional hazards regression model with an effect for treatment, stratifying for the following combinations of study participants' Baseline PGTCS frequency and Development from interactive response technology (IRT) (<= 2 per 28 days in the Combined Baseline Period and Pediatric, <= 2 per 28 days in the Combined Baseline Period and Adult, and > 2 per 28 days in the Combined Baseline Period). The reference group was Placebo.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Wald's method was used to calculate the p-value, Hazard Ratio (HR) and confidence intervals (CIs).
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.540
Confidence Interval (2-Sided) 95%
0.377 to 0.774
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Seizure Freedom for Primary Generalized Tonic Clonic (PGTC) Seizures During the 24-week Treatment Period From Visit 2 (Week 0) to Visit 10 (Week 24)
Hide Description A seizure-free day from primary generalized tonic clonic seizures (PGTCS) was defined as a day where no PGTCS were reported in the seizure diary and PGTCS were assessed, which was estimated using Kaplan-Meier (KM) methods.
Time Frame During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description

The Full Analysis Set (FAS) was a subset of the Safety Set (SS) that consisted of all study participants with at least 1 seizure diary assessment during the Treatment Period.

1 patient from the Lacosamide (FAS) group was randomized after the 125th event and did not appear in this analysis.

Arm/Group Title Placebo (FAS) Lacosamide (FAS)
Hide Arm/Group Description:

Placebo 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400mg/day for adult and pediatric participants >= 50 kg.

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants < 30 kg).

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the Full Analysis Set (FAS).

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400 mg/day for adult and pediatric participants with more or equal than (>=) 50 kilograms (kg).

Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants with less than (<) 30 kg).

Lasosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the FAS.

Overall Number of Participants Analyzed 121 118
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17.3
(10.3 to 24.3)
31.0
(22.4 to 39.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Lacosamide (FAS)
Comments The key secondary efficacy variable was evaluated using an extended Mantel-Haenszel testing procedure. Baseline PGTCS Frequency from Combined Baseline and development (age from interactive response technology (IRT)) were calculated from IRT.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.011
Comments Superiority of LCM vs Placebo p-value was based on a chi-square test on 1 degree of freedom.
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter KM seizure free of LCM vs Placebo
Estimated Value 14.1
Confidence Interval (2-Sided) 95%
3.2 to 25.1
Estimation Comments Stratified difference in proportion of subjects who are seizure-free from PGTCS on Lacosamide (FAS) vs Placebo (FAS).
3.Secondary Outcome
Title Time to the First Primary Generalized Tonic Clonic (PGTC) Seizure During the Treatment Period From Visit 2 (Week 0) to Visit 10 (Week 24)
Hide Description

The secondary efficacy variable was the time to the first primary generalized tonic clonic seizure (PGTCS) during the 24-week Treatment Period. Relative difference between groups (Lacosamide vs Placebo) was expressed as Hazard Ratio.

The indicated measured values are the observed number of events of first PGTCS in the treatment period which form the basis of the statistical analysis of the time to event analysis.

The hazard ratio compares 2 treatment groups for the times to the number of events for the combined treatment groups, and so both the number of events and the times until those events pertain to the computation of the hazard ratio.

A Hazard Ratio below 1 indicates time to second PGTCS was improved for LCM compared to Placebo.

Time Frame During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description

The Full Analysis Set (FAS) was a subset of the Safety Set (SS) that consisted of all study participants with at least 1 seizure diary assessment during the Treatment Period.

1 patient from the Lacosamide (FAS) group was randomized after the 125th event and did not appear in this analysis.

Arm/Group Title Placebo (FAS) Lacosamide (FAS)
Hide Arm/Group Description:

Placebo 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400mg/day for adult and pediatric participants >= 50 kg.

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants < 30 kg).

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the Full Analysis Set (FAS).

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400 mg/day for adult and pediatric participants with more or equal than (>=) 50 kilograms (kg).

Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants with less than (<) 30 kg).

Lasosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the FAS.

Overall Number of Participants Analyzed 121 118
Measure Type: Number
Unit of Measure: events
97 79
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Lacosamide (FAS)
Comments Comparison of LCM versus Placebo was based on a Cox proportional hazards regression model with an effect for treatment, stratifying for the following combinations of study participants' Baseline PGTCS frequency and Development from interactive response technology (IRT) (<= 2 per 28 days in the Combined Baseline Period and Pediatric, <= 2 per 28 days in the Combined Baseline Period and Adult, and > 2 per 28 days in the Combined Baseline Period). The reference group was Placebo.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.012
Comments Wald's method was used to calculate the p-value, Hazard Ratio (HR) and confidence intervals (CIs).
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.683
Confidence Interval (2-Sided) 95%
0.507 to 0.921
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With at Least One Adverse Event (AE) as Reported Spontaneously by the Subject and/or Caregiver or Observed by the Investigator
Hide Description An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational medicinal product (IMP), whether or not related to the IMP.
Time Frame From Visit 1 (Week -4) to End of Study Period (up to Week 36)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set (SS) was a subset of the Randomized Set (RS) and consisted of all study participants who had been treated with at least 1 dose of study medication, either LCM or Placebo.
Arm/Group Title Placebo (SS) Lacosamide (SS)
Hide Arm/Group Description:

Placebo 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400mg/day for adult and pediatric participants >= 50 kg.

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants < 30 kg).

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the Safety Set (SS).

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400 mg/day for adult and pediatric participants with more or equal than (>=) 50 kilograms (kg).

Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants with less than (<) 30 kg).

Lasosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the SS.

Overall Number of Participants Analyzed 121 121
Measure Type: Number
Unit of Measure: percentage of participants
81.8 82.6
5.Secondary Outcome
Title Plasma Concentrations of Lacosamide
Hide Description

Lacosamide plasma concentration was expressed in micrograms per milliliter (μg/mL).

Means and standard deviation (SD) were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint. Values Below Limit of Quantification (BLQ) were replaced by value of 0 in calculations of means and SDs.

Time Frame During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description

The Safety Set (SS) was a subset of the Randomized Set (RS) and consisted of all study participants who had been treated with at least 1 dose of study medication, either LCM or Placebo.

Data not collected from participants in Placebo (SS) Arm/Group.

Arm/Group Title Placebo (SS) Lacosamide (SS)
Hide Arm/Group Description:

Placebo 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400mg/day for adult and pediatric participants >= 50 kg.

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants < 30 kg).

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the Safety Set (SS).

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400 mg/day for adult and pediatric participants with more or equal than (>=) 50 kilograms (kg).

Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants with less than (<) 30 kg).

Lasosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the SS.

Overall Number of Participants Analyzed 0 121
Mean (Standard Deviation)
Unit of Measure: ug/mL
Visit 5, Week 6 (Titration) 8.610961  (3.705438)
Visit 10, Week 24 (Maintenance) 8.074427  (3.948749)
Early Termination Visit 8.138085  (4.913627)
Time Frame Adverse events were collected from Week 1 to End of Study Period (up to Week 36).
Adverse Event Reporting Description

TEAEs counts are for each study period: Treatment Period, Transition Period for participants who entered EP0012 (NCT02408549) and Taper Period followed by Safety Follow-up Period for participants not entering EP0012.

AEs reported for PBO participants during the Transition Period occur when they have switched to LCM.

 
Arm/Group Title Placebo (SS) Treatment Period Lacosamide (SS) Treatment Period Placebo (SS) Transition Period Lacosamide (SS) Transition Period Placebo (SS) Taper Period Lacosamide (SS) Taper Period Placebo (SS) Safety Follow-up Period Lacosamide (SS) Safety Follow-up Period
Hide Arm/Group Description

Participants received the following treatment during the Treatment Period (Week 0 to Week 24):

Placebo 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400mg/day for adult and pediatric participants >= 50 kg.

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants < 30 kg).

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the Safety Set (SS).

Participants received the following treatment during the Treatment Period (Week 0 to Week 24):

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day were allowed. Maximal dose 400 mg/day for adult and pediatric participants with more or equal than (>=) 50 kilograms (kg).

Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric participants with less than (<) 30 kg).

Lasosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric participants 30 kg to < 50 kg).

Participants formed the SS.

At the end of Visit 10 (Week 24)/ Early Termination (ET), study participants who completed the study may have been eligible to participate in an open-label extension study (EP0012). Study participants who chose to enroll in the open-label extension study proceeded to a blinded 4-week Transition Period.

Participants randomized to Placebo in the Treatment Period transitioned to double-blind Lacosamide:

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 100 mg/day until final dose of 400 mg/day at Week 4 for adult and pediatric participants >= 50 kg.

Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day at Week 1. Weekly increase in steps of 2 mg/kg/day until final dose of 8 mg/kg/day at Week 4 for pediatric participants < 30 kg and 0 kg to < 50 kg.

Participants formed the SS.

At the end of Visit 10 (Week 24)/ Early Termination (ET), study participants who completed the study may have been eligible to participate in an open-label extension study (EP0012). Study participants who chose to enroll in the open-label extension study proceeded to a blinded 4-week Transition Period.

Participants randomized to Lacosaminde in the Treatment Period continued to receive double-blind Lacosamide:

Lacosamide 50 mg tablets: minim (min) 300 mg/day to maximum (max) 400 mg/day from Week 1 to Week 3 and final dose of 400 mg/day at Week 4 for adult and pediatric participants >= 50 kg.

Lacosamide oral solution 10 mg/ml: min 8 mg/kg/day to max 12 mg/kg/day from Week 1 to Week 4 for pediatric participants < 30 kg.

Lacosamide oral solution 10 mg/ml: min 6 mg/kg/day to max 8 mg/kg/day from Week 1 to Week 3 and final dose of 8 mg/kg/day at Week 4 for pediatric participants 30 kg to < 50 kg.

Participants formed the SS.

Study participants completing Visit 10 (Week 24) or the ET Visit who chose not to continue in EP0012 must have completed an up to 4 weeks blinded taper followed by the End of Taper Visit.

Participants randomized to Placebo in the Treatment Period continued to receive Placebo:

Placebo 50 mg tablets: starting with maximum dose achieved during the Treatment Period. Weekly decrease in steps of 100 mg/day until no treatment received for adult and pediatric participants >= 50 kg.

Placebo oral solution 10 mg/ml: starting with maximum dose achieved during the Treatment Period. Weekly decrease in steps of 2 mg/kg/day or 3 mg/kg/day until no treatment received for pediatric participants < 30 kg and 0 kg to < 50 kg.

Participants formed the SS.

Study participants completing Visit 10 (Week 24) or the ET Visit who chose not to continue in EP0012 must have completed an up to 4 weeks blinded taper followed by the End of Taper Visit.

Participants randomized to Lacosamide in the Treatment Period continued to receive Lacosamide:

Lacosamide 50 mg tablets: starting with maximum dose achieved during the Treatment Period. Weekly decrease in steps of 100 mg/day until no treatment received for adult and pediatric participants >= 50 kg.

Lacosamide oral solution 10 mg/ml: starting with maximum dose achieved during the Treatment Period. Weekly decrease in steps of 2 mg/kg/day or 3 mg/kg/day until no treatment received for pediatric participants < 30 kg and 0 kg to < 50 kg.

Participants formed the SS.

There was a 30-day (-1/+3 days) Safety Follow-up Period for study participants who completed the End of Taper Visit. The Safety Follow-up Period consisted of a clinic visit 2 weeks after the End of Taper Visit followed 2 weeks later by a telephone contact (TC).

Participants did not receive any treatment during this period. Participants formed the SS.

There was a 30-day (-1/+3 days) Safety Follow-up Period for study participants who completed the End of Taper Visit. The Safety Follow-up Period consisted of a clinic visit 2 weeks after the End of Taper Visit followed 2 weeks later by a telephone contact (TC).

Participants did not receive any treatment during this period. Participants formed the SS.

All-Cause Mortality
Placebo (SS) Treatment Period Lacosamide (SS) Treatment Period Placebo (SS) Transition Period Lacosamide (SS) Transition Period Placebo (SS) Taper Period Lacosamide (SS) Taper Period Placebo (SS) Safety Follow-up Period Lacosamide (SS) Safety Follow-up Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/121 (0.00%)      0/121 (0.00%)      0/108 (0.00%)      0/101 (0.00%)      0/7 (0.00%)      0/9 (0.00%)      0/10 (0.00%)      0/11 (0.00%)    
Hide Serious Adverse Events
Placebo (SS) Treatment Period Lacosamide (SS) Treatment Period Placebo (SS) Transition Period Lacosamide (SS) Transition Period Placebo (SS) Taper Period Lacosamide (SS) Taper Period Placebo (SS) Safety Follow-up Period Lacosamide (SS) Safety Follow-up Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/121 (3.31%)      8/121 (6.61%)      0/108 (0.00%)      3/101 (2.97%)      0/7 (0.00%)      0/9 (0.00%)      1/10 (10.00%)      1/11 (9.09%)    
Gastrointestinal disorders                 
Abdominal pain * 1  0/121 (0.00%)  0 1/121 (0.83%)  1 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Nausea * 1  0/121 (0.00%)  0 1/121 (0.83%)  1 0/108 (0.00%)  0 1/101 (0.99%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Vomiting * 1  0/121 (0.00%)  0 1/121 (0.83%)  1 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
General disorders                 
Asthenia * 1  0/121 (0.00%)  0 1/121 (0.83%)  1 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Infections and infestations                 
Upper respiratory tract infection * 1  1/121 (0.83%)  1 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Injury, poisoning and procedural complications                 
Contusion * 1  0/121 (0.00%)  0 1/121 (0.83%)  1 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Femur fracture * 1  1/121 (0.83%)  1 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Road traffic accident * 1  1/121 (0.83%)  1 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Head injury * 1  0/121 (0.00%)  0 0/121 (0.00%)  0 0/108 (0.00%)  0 1/101 (0.99%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Investigations                 
Transaminases increased * 1  0/121 (0.00%)  0 1/121 (0.83%)  1 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Liver function test abnormal * 1  1/121 (0.83%)  1 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Musculoskeletal and connective tissue disorders                 
Pain in extremity * 1  0/121 (0.00%)  0 1/121 (0.83%)  1 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Nervous system disorders                 
Dizziness * 1  0/121 (0.00%)  0 2/121 (1.65%)  2 0/108 (0.00%)  0 1/101 (0.99%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Somnolence * 1  0/121 (0.00%)  0 2/121 (1.65%)  2 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Grand mal convulsion * 1  0/121 (0.00%)  0 1/121 (0.83%)  1 0/108 (0.00%)  0 1/101 (0.99%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Headache * 1  0/121 (0.00%)  0 1/121 (0.83%)  1 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Status epilepticus * 1  0/121 (0.00%)  0 1/121 (0.83%)  1 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Clonic convulsion * 1  0/121 (0.00%)  0 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0
Surgical and medical procedures                 
Abortion induced * 1  0/121 (0.00%)  0 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1
1
Term from vocabulary, MedDRA16.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo (SS) Treatment Period Lacosamide (SS) Treatment Period Placebo (SS) Transition Period Lacosamide (SS) Transition Period Placebo (SS) Taper Period Lacosamide (SS) Taper Period Placebo (SS) Safety Follow-up Period Lacosamide (SS) Safety Follow-up Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   41/121 (33.88%)      60/121 (49.59%)      27/108 (25.00%)      5/101 (4.95%)      3/7 (42.86%)      2/9 (22.22%)      0/10 (0.00%)      0/11 (0.00%)    
Ear and labyrinth disorders                 
Vertigo * 1  2/121 (1.65%)  2 8/121 (6.61%)  8 3/108 (2.78%)  4 1/101 (0.99%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Gastrointestinal disorders                 
Nausea * 1  7/121 (5.79%)  7 11/121 (9.09%)  12 2/108 (1.85%)  3 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Vomiting * 1  1/121 (0.83%)  3 7/121 (5.79%)  10 3/108 (2.78%)  5 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Dyspepsia * 1  0/121 (0.00%)  0 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 1/7 (14.29%)  1 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
General disorders                 
Fatigue * 1  6/121 (4.96%)  6 8/121 (6.61%)  8 2/108 (1.85%)  2 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Infections and infestations                 
Nasopharyngitis * 1  4/121 (3.31%)  4 8/121 (6.61%)  12 2/108 (1.85%)  2 1/101 (0.99%)  1 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Upper respiratory tract infection * 1  0/121 (0.00%)  0 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 1/7 (14.29%)  1 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Injury, poisoning and procedural complications                 
Laceration * 1  0/121 (0.00%)  0 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0
Investigations                 
Hepatic enzyme increased * 1  0/121 (0.00%)  0 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 1/7 (14.29%)  1 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Nervous system disorders                 
Dizziness * 1  7/121 (5.79%)  7 26/121 (21.49%)  34 10/108 (9.26%)  10 3/101 (2.97%)  3 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Somnolence * 1  17/121 (14.05%)  17 18/121 (14.88%)  19 7/108 (6.48%)  7 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Headache * 1  12/121 (9.92%)  13 16/121 (13.22%)  18 5/108 (4.63%)  5 0/101 (0.00%)  0 0/7 (0.00%)  0 0/9 (0.00%)  0 0/10 (0.00%)  0 0/11 (0.00%)  0
Drooling * 1  0/121 (0.00%)  0 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0
Grand mal convulsion * 1  0/121 (0.00%)  0 0/121 (0.00%)  0 0/108 (0.00%)  0 0/101 (0.00%)  0 0/7 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0
1
Term from vocabulary, MedDRA16.1
*
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, Inc. )
ClinicalTrials.gov Identifier: NCT02408523    
Other Study ID Numbers: SP0982
2011-003100-21 ( EudraCT Number )
First Submitted: March 31, 2015
First Posted: April 3, 2015
Results First Submitted: April 3, 2020
Results First Posted: April 16, 2020
Last Update Posted: May 20, 2020