Epilepsy
Conditions
Keywords
Lacosamide, Epilepsy, Levetiracetam, Sodium Channel Blockers
Brief summary
The main purpose of this study is to evaluate the effectiveness of the study drug lacosamide (200-600 mg/day) when added to a stable dose of levetiracetam (1000-3000 mg/day) with withdrawal of the concomitant sodium channel blocking-antiepileptic drug (AEDs) in subjects not well controlled on their current regimen.
Interventions
DRUGLacosamide
50 mg and 100 mg lacosamide tablets will be combined and taken in two equal doses per day to provide the required total daily dosage of 100 - 600 mg/day. Subjects were titrated to a minimum of 200 mg/ day during the Treatment Period. Maximum duration of study drug administration is approximately 23 weeks.
Sponsors
UCB Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is male or female, at least 18 years of age * Subject has a diagnosis of epilepsy with partial-onset seizures according to the International Classification of Epileptic Seizures (1981) * Subject is taking levetiracetam (LEV) in combination with 1 sodium channel blocking antiepileptic drug (defined as carbamazepine, lamotrigine, oxcarbazepine, phenytoin, or eslicarbazepine) as adjunctive treatment for epilepsy * The minimum required seizure frequency during the 8-week Retrospective Seizure Baseline is on average ≥ 2 partial-onset seizures per 28 days with at least 1 seizure per 4 week period within the 8-week Retrospective Seizure Baseline. Additionally, subjects must experience at least 1 seizure during the 4-week Prospective Seizure Baseline * Subject has been maintained on a stable dose of LEV and a sodium channel blocking antiepileptic drug (SCB-AED) for at least 4 weeks prior to the Screening Visit (Visit 1) and during the 4-week Prospective Seizure Baseline * The minimum required seizure frequency during the 8-week Retrospective Seizure Baseline is on average ≥ 2 partial-onset seizures per 28 days (based on investigator assessment of subject report) with at least 1 seizure per 4 week period within the 8-week Retrospective Seizure Baseline * Subject has been maintained on a stable dose of levetiracetam (LEV) and a sodium channel blocking antiepileptic drug (SCB-AED) for at least 4 weeks prior to the Screening Visit (Visit 1) and during the 4-week Prospective Seizure Baseline, with or without additional concurrent stable vagal nerve stimulation (VNS). The VNS must have been in place for at least 6 months prior to the Screening Visit (Visit 1) with constant settings for at least 4-weeks prior to the Screening Visit (Visit 1) and throughout the duration of the study
Exclusion criteria
* Previous use of lacosamide * History of alcohol or drug abuse * History of seizure disorder characterized primarily by isolated auras * History of primary generalized seizures * History of status epilepticus within the 12-months * History of clustering seizures * Nonepileptic events, including pseudoseizures that could be confused with seizures * History of any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize the subject's health or would compromise the subject's ability to participate in this study * Lifetime history of suicide attempt, or suicidal ideation in the past 6 months * Hypersensitivity to any component of lacosamide (LCM) * History of acute or sub-acute progressive central nervous system disease * History of severe anaphylactic reaction or serious blood dyscrasias * Impaired renal function (ie, Creatinine Clearance (CLcr) is lower than 30 mL/min) at Visit 1 * History of sick sinus syndrome without a pacemaker, or atrioventricular (AV) block, or subject has any other clinically significant electrocardiogram (ECG) abnormalities * History sodium channelopathy, such as Brugada syndrome * History of myocardial infarction in the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention at the End of the 21-week Treatment Period | Duration of the Treatment Period (21 Weeks) | Retention is a summary measure that integrates both the patient's and clinician's assessment of efficacy and tolerability in epilepsy clinical studies to provide a measure of effectiveness. |
Countries
Australia, Bulgaria, Denmark, France, Germany, Romania, Spain, Sweden, United States
Participant flow
Recruitment details
The recruitment for the SP0980 study began in December 2011. It concluded in January 2014. This was a multicenter study with subjects enrolled by 30 sites across North America, 12 in Western Europe, 10 in Eastern Europe, and 2 in Oceania.
Pre-assignment details
The participant flow consists of subjects in the Safety Set (SS). The SS is all subjects who received at least 1 dose of lacosamide.
Participants by arm
| Arm | Count |
|---|---|
| Lacosamide Lacosamide will be added to levetiracetam while withdrawing the sodium channel blocking antiepileptic drug (AED).
Lacosamide: 50 mg and 100 mg lacosamide tablets will be combined and taken in two equal doses per day to provide the required total daily dosage of 100 - 600 mg/day. Subjects were titrated to a minimum of 200 mg/ day during the Treatment Period.
Maximum duration of study drug administration is approximately 23 weeks. | 120 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Lack of Compliance | 1 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Low White Blood Cell Count | 1 |
| Overall Study | Moving Overseas | 1 |
| Overall Study | Protocol Violation | 6 |
| Overall Study | Subject Protocol Non-compliant | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Lacosamide |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 114 Participants |
| Age, Continuous | 39.7 years STANDARD_DEVIATION 12.6 |
| BMI | 27.00 kilogram/ square meter STANDARD_DEVIATION 6.45 |
| Ethnicity Hispanic or Latino | 17 participants |
| Ethnicity Not Hispanic or Latino | 103 participants |
| Height | 168.02 centimeters STANDARD_DEVIATION 10.55 |
| Racial Group American Indian/Alaskan Native | 1 participants |
| Racial Group Asian | 3 participants |
| Racial Group Black | 8 participants |
| Racial Group Native Hawaiian or other Pacific Islander | 0 participants |
| Racial Group Other/Mixed | 12 participants |
| Racial Group White | 96 participants |
| Sex: Female, Male Female | 74 Participants |
| Sex: Female, Male Male | 46 Participants |
| Weight | 76.39 kilograms STANDARD_DEVIATION 19.98 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 52 / 120 |
| serious Total, serious adverse events | 8 / 120 |
Outcome results
Primary
Retention at the End of the 21-week Treatment Period
Retention is a summary measure that integrates both the patient's and clinician's assessment of efficacy and tolerability in epilepsy clinical studies to provide a measure of effectiveness.
Time frame: Duration of the Treatment Period (21 Weeks)
Population: The primary analysis consists of subjects in the Safety Set (SS). The SS is all subjects who received at least 1 dose of lacosamide.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lacosamide | Retention at the End of the 21-week Treatment Period | 73.3 percentage of participants |
Comparison: Analyses of the primary efficacy variable will be descriptive only. No hypothesis tests are planned.~The number and percentage of subjects remaining in the study through the 21-Week Treatment Period will be calculated. Subjects with retention will be counted in the numerator. All subjects in the relevant population will be used as the denominator.~This percentage will be known as the retention rate, along with the 95 % confidence interval based on the normal approximation.95% CI: [65.42, 81.25]