Epilepsy
Conditions
Keywords
Lacosamide, Vimpat, UCB, Epilepsy, Partial Onset Seizures, Pediatric
Brief summary
Study to evaluate the efficacy of Lacosamide (LCM) administered in addition to 1 to ≤3 other Anti-Epileptic Drugs in subjects with epilepsy ≥4 years to \<17 years of age who currently have uncontrolled partial onset seizures.
Detailed description
The primary objective of this study is to evaluate the efficacy of LCM administered concomitantly with 1 to ≤3 Anti-Epileptic Drugs (AEDs) in subjects with epilepsy ≥4 years to \<17 years of age who currently have uncontrolled partial onset seizures. The secondary objective is to evaluate the safety and tolerability of LCM in subjects ≥4 years to \<17 years of age. An additional objective is to evaluate the pharmacokinetics (PK) of LCM in subjects ≥4 years to \<17 years of age.
Interventions
DRUGLacosamide
Subjects \<30 kg (LCM oral solution): 4 mg/kg - 6 mg/kg BID ( 8mg/kg/day - 12 mg/kg/day) Subjects ≥30 kg to \<50 kg (LCM oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day) Subjects ≥50 kg (LCM tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day)
OTHERPlacebo
Subjects \<30 kg (placebo oral solution): 4 mg/kg - 6 mg/kg BID (8 mg/kg/day - 12 mg/kg/day) Subjects ≥30 kg to \<50 kg (placebo oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day) Subjects ≥50 kg (placebo tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day)
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the parent(s) or legal representative. The Informed Consent form or a specific Assent form, where required, will be signed and dated by minors * Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the investigator * Subject is male or female from ≥4 years to \<17 years of age * Subject has a diagnosis of Epilepsy with partial-onset seizures. The results of ≥1 prior electroencephalogram (EEG) AND 1 prior magnetic resonance imaging/computerized tomography scan should be consistent with the above diagnosis * Subject has been observed to have uncontrolled partial-onset seizures after an adequate course of treatment (in the opinion of the investigator) with ≥2 Anti-Epileptic Drugs (AEDs) (concurrently or sequentially) * Subject must have been observed to have on average ≥2 partial onset seizures per 28 days with seizure free phase no longer than 21 days in the 8 week period prior to entry into the Baseline Period. During this study, subjects must have reported ≥2 partial onset seizures during the 8 week prospective Baseline Period to be eligible for randomization at Visit 2. (Note: In the case of simple partial onset seizures, only those seizures with motor signs will be counted towards meeting the inclusion criterion.) * Subject is on a stable dosage regimen of 1 to ≤3 AEDs. The daily dosage regimen of concomitant AED therapy must be kept constant for a period of ≥4 weeks prior to the Baseline Period * Vagal nerve stimulation (VNS) is allowed and will not be counted as a concomitant AED. The VNS device must be implanted for ≥6 months before Visit 1, and the device settings must be stable for ≥4 weeks before Visit 1 and be kept stable during the Baseline Period. Use of the VNS device magnet is allowed
Exclusion criteria
* Subject has previously participated in this study or subject has been assigned to Lacosamide (LCM) in a previous LCM study * Subject has participated in another study of an investigational medicinal product (IMP) or a medical device within ≤2 months of Visit 1 or is currently participating in another study of an IMP or a medical device * Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study * Subject ≥6 years of age has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Columbia Suicide Severity Rating Scale (C SSRS) at Screening * Subject has a known hypersensitivity to any component of the IMP or has ever received LCM * Female subject who is pregnant or nursing, and/or a female subject of childbearing potential who is not surgically sterile or does not practice 1 highly effective method of contraception (according to International Conference on Harmonisation \[ICH\] guidance defined as those that result in a failure rate of less than 1% per year when used consistently and correctly), unless sexually abstinent, for the duration of the study. Female subject of childbearing potential taking enzyme inducing antiepileptic drugs (EI AEDs: carbamazepine, phenytoin, barbiturates, primidone, topiramate, oxcarbazepine) who is not surgically sterile or does not practice 1 highly effective method of contraception according to the WHO recommendation (ie, depot medroxyprogesterone acetate, norethisterone enantate, intrauterine devices, combined injectables, and progestogen implants) with administration of EI AEDs OR does not practice 2 combined methods of contraception (ie, combined hormonal contraception plus barrier method with spermicidal agent), unless sexually abstinent, for the duration of the study * Subject has a medical condition that could be expected in the opinion of the investigator to interfere with drug absorption, distribution, metabolism, or excretion * Subject has experienced febrile seizures exclusively. The occurrence of febrile seizures in addition to other unprovoked seizures is not exclusionary * Subject is on a ketogenic or other specialized diet. If the subject was on a specialized diet in the past, they must be off the diet for ≥2 months prior to the Baseline Period * Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin level ≥2 times the upper limit of normal (ULN), or creatinine clearance less than 30 mL/min * Subject has a clinically relevant ECG abnormality, in the opinion of the investigator (eg, second or third degree heart block at rest or a corrected QT interval \[QTc\] greater than 450 ms) * Subject has hemodynamically significant congenital heart disease * Subject has an arrhythmic heart condition requiring medical therapy * Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias * Subject has nonepileptic events that could be confused with seizures * Subject has a current diagnosis of Lennox-Gastaut syndrome, primary generalized epilepsy, mixed seizure disorder (partial and primarily generalized seizures), or purely nocturnal seizures * Subject has a history of convulsive status epilepticus ≤2 months prior to the Baseline Period * Subject has been treated with vigabatrin and experienced any vision loss. Subjects who have received vigabatrin in the past must have documentation of an assessment for vision loss prior to study entry or documentation of why visual field testing cannot be performed * Subject has been treated with felbamate and has experienced any serious toxicity issues (defined as liver failure, aplastic anemia) with this treatment. Subjects treated with felbamate for \<12 months are excluded. Note: any subject who has been treated with felbamate for ≥12 months and has not experienced serious toxicity issues is eligible * Subject has a medically documented history of alcohol or drug abuse * Subject has a known cardiac sodium channelopathy, such as Brugada syndrome * Subject has an acute or sub acutely progressive central nervous system disease. Subject has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease (malignant brain tumor or Rasmussen Syndrome)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Partial Onset Seizure (POS) Frequency Per 28 Days From Baseline to the Maintenance Period | Baseline to Week 16 (or last value on treatment) | The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period | Baseline to Week 16 (or last value on treatment) | Proportion of subjects is presented as percentage of participants. A \>=25%-\<50% response in the Maintenance Period is defined as \>=25% to \<50% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. A \>=50%-\<=75% response in the Maintenance Period is defined as \>=50% to \<=75% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. A 75% response in the Maintenance Period is defined as \>75% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. |
| Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | Baseline to Week 16 (or last value on treatment) | The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline. |
| Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | Baseline to Week 16 (or last value on treatment) | Proportion of subjects is presented as percentage of participants. A \>=25%-\<50% response in the Treatment Period is defined as \>=25% to \<50% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. A \>=50%-\<=75% response in the Treatment Period is defined as \>=50% to \<=75% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. A 75% response in the Treatment Period is defined as \>75% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. |
| Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Secondary Generalized Seizures | Baseline to Week 16 (or last value on treatment) | The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline. |
| Proportion of Subjects Experiencing no Change in Partial Onset Seizure Frequency (Between <25 % Reduction and <25 % Increase) Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | Baseline to Week 16 (or last value on treatment) | Proportion of subjects is presented as percentage of participants. No change is defined as between \<25% reduction and \<25% increase in POS frequency per 28 days from Baseline to the entire Treatment Period, otherwise not between \<25% reduction and \<25% increase is defined as a change. |
| Proportion of Responders Where a Responder is Defined as a Participant With >= 50% Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period | Baseline to Week 16 (or last value on treatment) | Proportion of responders is presented as percentage of participants. A responder is a subject experiencing a 50 % or greater reduction in partial onset seizure frequency per 28 days from Baseline to the Maintenance Period. |
| Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Simple Partial Seizures | Baseline to Week 16 (or last value on treatment) | The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline. |
| Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Complex Partial Seizures | Baseline to Week 16 (or last value on treatment) | The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline. |
| Proportion of Seizure Free Days During the Maintenance Period for Subjects Who Completed the Maintenance Period | Week 7 to Week 16 | The proportion of seizure free days is calculated as (days with number of seizures = 0) divided by (days with recorded data in the subject diary), where 'days with recorded data in the subject diary' excludes any days where 'Not Done' is recorded. |
| Proportion of Subjects Who Achieved Seizure Free Status (Yes/no) for Subjects Who Completed the Maintenance Period | Week 7 to Week 16 | The proportion of seizure free days is calculated as (days with number of seizures = 0) divided by (days with recorded data in the subject diary), where 'days with recorded data in the subject diary' excludes any days where 'Not Done' is recorded. |
| Proportion of Subjects Experiencing an Increase in Partial Onset Seizure Frequency Per 28 Days of >=25 % From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | Baseline to Week 16 (or last value on treatment) | Proportion of subjects is presented as percentage of participants. An increase is defined as a \>=25% increase in POS frequency per 28 days from Baseline to the entire Treatment Period, otherwise \<25% increase is defined as no increase. |
Countries
Argentina, Australia, Belgium, Bulgaria, Colombia, Croatia, Czechia, Estonia, Georgia, Hungary, Israel, Italy, Latvia, Lithuania, Mexico, Montenegro, Poland, Romania, Russia, Serbia, Slovakia, Slovenia, South Korea, Taiwan, Thailand, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study started to enroll patients in August 2013 and concluded in January 2017.
Pre-assignment details
The Participant Flow refers to the Safety Set which included all randomized subjects who took at least 1 dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| Placebo This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets. | 172 |
| Lacosamide This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing \<30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing \>=30kg to \<50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing \>=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study. | 171 |
| Total Title | 343 |
| Total | 686 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 7 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Non Compliance Of Child | 0 | 1 |
| Overall Study | Non Compliance Of The Parent | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | The Excessive Use Of Rescue Medication | 0 | 1 |
| Overall Study | Use Of Prohibited Medication | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Placebo | Lacosamide | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 172 Participants | 171 Participants | 343 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.9 years STANDARD_DEVIATION 3.5 | 10.5 years STANDARD_DEVIATION 3.6 | 10.7 years STANDARD_DEVIATION 3.5 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 35 Participants | 25 Participants | 60 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Other/Mixed | 6 Participants | 6 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 129 Participants | 138 Participants | 267 Participants |
| Sex: Female, Male Female | 73 Participants | 80 Participants | 153 Participants |
| Sex: Female, Male Male | 99 Participants | 91 Participants | 190 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 172 | 0 / 171 |
| other Total, other adverse events | 61 / 172 | 85 / 171 |
| serious Total, serious adverse events | 13 / 172 | 11 / 171 |
Outcome results
Primary
Change in Partial Onset Seizure (POS) Frequency Per 28 Days From Baseline to the Maintenance Period
The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.
Time frame: Baseline to Week 16 (or last value on treatment)
Population: The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with available data were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (FAS) | Change in Partial Onset Seizure (POS) Frequency Per 28 Days From Baseline to the Maintenance Period | -1.55 Seizures per 28 days |
| Lacosamide (FAS) | Change in Partial Onset Seizure (POS) Frequency Per 28 Days From Baseline to the Maintenance Period | -3.05 Seizures per 28 days |
p-value: =0.000395% CI: [16.342, 44.277]ANCOVA
Secondary
Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.
Time frame: Baseline to Week 16 (or last value on treatment)
Population: The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with available data were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (FAS) | Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | -1.22 Seizures per 28 days |
| Lacosamide (FAS) | Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | -2.46 Seizures per 28 days |
Secondary
Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Complex Partial Seizures
The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.
Time frame: Baseline to Week 16 (or last value on treatment)
Population: The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with Complex Partial Seizures were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (FAS) | Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Complex Partial Seizures | -0.98 Seizures per 28 days |
| Lacosamide (FAS) | Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Complex Partial Seizures | -2.06 Seizures per 28 days |
Secondary
Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Secondary Generalized Seizures
The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.
Time frame: Baseline to Week 16 (or last value on treatment)
Population: The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with Secondary Generalized Seizures were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (FAS) | Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Secondary Generalized Seizures | -1.0 Seizures per 28 days |
| Lacosamide (FAS) | Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Secondary Generalized Seizures | -2.81 Seizures per 28 days |
Secondary
Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Simple Partial Seizures
The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.
Time frame: Baseline to Week 16 (or last value on treatment)
Population: The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with Simple Partial Seizures were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (FAS) | Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Simple Partial Seizures | -1.14 Seizures per 28 days |
| Lacosamide (FAS) | Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Simple Partial Seizures | -1.25 Seizures per 28 days |
Secondary
Proportion of Responders Where a Responder is Defined as a Participant With >= 50% Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period
Proportion of responders is presented as percentage of participants. A responder is a subject experiencing a 50 % or greater reduction in partial onset seizure frequency per 28 days from Baseline to the Maintenance Period.
Time frame: Baseline to Week 16 (or last value on treatment)
Population: The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with response data have been included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Proportion of Responders Where a Responder is Defined as a Participant With >= 50% Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period | 33.3 percentage of participants |
| Lacosamide (FAS) | Proportion of Responders Where a Responder is Defined as a Participant With >= 50% Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period | 52.9 percentage of participants |
Secondary
Proportion of Seizure Free Days During the Maintenance Period for Subjects Who Completed the Maintenance Period
The proportion of seizure free days is calculated as (days with number of seizures = 0) divided by (days with recorded data in the subject diary), where 'days with recorded data in the subject diary' excludes any days where 'Not Done' is recorded.
Time frame: Week 7 to Week 16
Population: Percentages are based on the number of subjects in the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects who completed the Maintenance Period have been included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Proportion of Seizure Free Days During the Maintenance Period for Subjects Who Completed the Maintenance Period | 0.65 days | Standard Deviation 0.35 |
| Lacosamide (FAS) | Proportion of Seizure Free Days During the Maintenance Period for Subjects Who Completed the Maintenance Period | 0.71 days | Standard Deviation 0.32 |
Secondary
Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period
Proportion of subjects is presented as percentage of participants. A \>=25%-\<50% response in the Maintenance Period is defined as \>=25% to \<50% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. A \>=50%-\<=75% response in the Maintenance Period is defined as \>=50% to \<=75% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. A 75% response in the Maintenance Period is defined as \>75% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period.
Time frame: Baseline to Week 16 (or last value on treatment)
Population: The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period | >=25% - <50% | 14.7 percentage of participants |
| Placebo (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period | >=50% - <=75% | 17.1 percentage of participants |
| Placebo (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period | >75% | 15.9 percentage of participants |
| Lacosamide (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period | >=25% - <50% | 11.8 percentage of participants |
| Lacosamide (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period | >=50% - <=75% | 21.8 percentage of participants |
| Lacosamide (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period | >75% | 31.2 percentage of participants |
Secondary
Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
Proportion of subjects is presented as percentage of participants. A \>=25%-\<50% response in the Treatment Period is defined as \>=25% to \<50% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. A \>=50%-\<=75% response in the Treatment Period is defined as \>=50% to \<=75% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. A 75% response in the Treatment Period is defined as \>75% reduction in POS frequency per 28 days from Baseline to end of Treatment Period.
Time frame: Baseline to Week 16 (or last value on treatment)
Population: The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | >=50% - <=75% | 20.6 percentage of participants |
| Placebo (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | >75% | 8.8 percentage of participants |
| Placebo (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | >=25% - <50% | 15.3 percentage of participants |
| Lacosamide (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | >=50% - <=75% | 20.6 percentage of participants |
| Lacosamide (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | >75% | 23.5 percentage of participants |
| Lacosamide (FAS) | Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | >=25% - <50% | 16.5 percentage of participants |
Secondary
Proportion of Subjects Experiencing an Increase in Partial Onset Seizure Frequency Per 28 Days of >=25 % From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
Proportion of subjects is presented as percentage of participants. An increase is defined as a \>=25% increase in POS frequency per 28 days from Baseline to the entire Treatment Period, otherwise \<25% increase is defined as no increase.
Time frame: Baseline to Week 16 (or last value on treatment)
Population: The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with response data have been included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Proportion of Subjects Experiencing an Increase in Partial Onset Seizure Frequency Per 28 Days of >=25 % From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | 23.1 percentage of participants |
| Lacosamide (FAS) | Proportion of Subjects Experiencing an Increase in Partial Onset Seizure Frequency Per 28 Days of >=25 % From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | 18.8 percentage of participants |
Secondary
Proportion of Subjects Experiencing no Change in Partial Onset Seizure Frequency (Between <25 % Reduction and <25 % Increase) Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
Proportion of subjects is presented as percentage of participants. No change is defined as between \<25% reduction and \<25% increase in POS frequency per 28 days from Baseline to the entire Treatment Period, otherwise not between \<25% reduction and \<25% increase is defined as a change.
Time frame: Baseline to Week 16 (or last value on treatment)
Population: The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with response data have been included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Proportion of Subjects Experiencing no Change in Partial Onset Seizure Frequency (Between <25 % Reduction and <25 % Increase) Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | 32.0 percentage of participants |
| Lacosamide (FAS) | Proportion of Subjects Experiencing no Change in Partial Onset Seizure Frequency (Between <25 % Reduction and <25 % Increase) Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) | 20.6 percentage of participants |
Secondary
Proportion of Subjects Who Achieved Seizure Free Status (Yes/no) for Subjects Who Completed the Maintenance Period
The proportion of seizure free days is calculated as (days with number of seizures = 0) divided by (days with recorded data in the subject diary), where 'days with recorded data in the subject diary' excludes any days where 'Not Done' is recorded.
Time frame: Week 7 to Week 16
Population: Percentages are based on the number of subjects in the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects who completed the Maintenance Period have been included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Proportion of Subjects Who Achieved Seizure Free Status (Yes/no) for Subjects Who Completed the Maintenance Period | 9.7 percentage of participants |
| Lacosamide (FAS) | Proportion of Subjects Who Achieved Seizure Free Status (Yes/no) for Subjects Who Completed the Maintenance Period | 15.1 percentage of participants |