Partial Epilepsies
Conditions
Keywords
Epilepsy Treatment, Anti-epileptic drugs, Seizures, Vimpat
Brief summary
To evaluate the efficacy and safety of oral Lacosamide as first add on treatment in subjects with uncontrolled partial-onset seizures after prior treatment with a monotherapy Antiepileptic Drug (AED) regimen compared to subjects who have received treatment with at least 2 AEDs.
Detailed description
The study consisted of 3 Periods: Period 1: a 1-week Screening Phase, Period 2: a 30-week Treatment Phase (consisting of a 6-week Titration Phase and a 24-week Maintenance Phase), and Period 3: a 3-week Taper/Safety Follow-Up Phase.
Interventions
DRUGLacosamide
Oral Lacosamide: Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week
Sponsors
UCB Pharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Group 1: * Subject has a diagnosis of epilepsy with simple partial seizures (motor component) and/or complex partial seizures with or without secondary generalization * Currently taking adequate monotherapy (defined as a single Antiepileptic Drug (AED) for at least 28 days prior to Screening) and has no history of AED polytherapy. Prior use of rescue medication (short-term intermittent use) is acceptable * Epilepsy diagnosis should be ≤24 months at the time of the Screening Visit * The minimum allowed seizure frequency at any time during the 12 weeks prior to the Screening Visit is ≥3 partial-onset seizures Group 2: * Subject has a diagnosis of epilepsy with simple partial seizures (motor component) and/or complex partial seizures with or without secondary generalization * Currently taking 1 to 3 AEDs, and has tried at least 2 prior AED treatment regimens (concurrently or sequentially) * Epilepsy diagnosis should be ≥5 years at the time of the Screening Visit * The minimum allowed seizure frequency during the 12 weeks prior to the Screening Visit is ≥1 partial-onset seizure per 28 days
Exclusion criteria
* Previous use of Lacosamide * History of seizure disorder characterized primarily by isolated auras * History of primary generalized seizures * History of status epilepticus within last 12-months * History of cluster seizures during the 12 week period prior to Visit 1 * Nonepileptic events, including pseudoseizures that could be confused with seizure * Lifetime history of suicide attempt or suicidal ideation in the past 6 months * Hypersensitivity to any component of Lacosamide * History of drug or alcohol abuse * History of an acute or subacutely progressive Central Nervous System (CNS) disease * Undergone cranial surgery within the last year prior to study entry * Concomitant treatment of Felbamate or previous Felbamate therapy within the last 6 months * Prior or concomitant Vigabatrin use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects Who Achieved Seizure-free Status During the First 12 Weeks of the Maintenance Phase | From Week 7 (end of Week 6) to end of Week 18 | A subject will be considered seizure-free if the subject completes the first 12 weeks of the Maintenance Phase, reports zero seizures, and has no seizure data missing for any day during the period of time. This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn. |
Countries
Austria, Bulgaria, Czechia, Denmark, Finland, France, Greece, Italy, Mexico, Romania, Russia, Spain, Switzerland, Turkey (Türkiye), United States
Participant flow
Recruitment details
An estimated 656 subjects were to be enrolled in the study at approximately 130 sites in the US, Europe, and the rest of the world.
Pre-assignment details
Overall 461 subjects were enrolled. The Participant Flow refers to the Safety Set (SS) which was defined as all enrolled subjects who took at least 1 dose of Lacosamide. Reasons for discontinuation were only calculated for the SS. 456 subjects were included in the Safety Set.
Participants by arm
| Arm | Count |
|---|---|
| First Add-on Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis \< or = 24 months at Screening.
Lacosamide: oral tablet
Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid
Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid
Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week | 96 |
| Later-Add-on Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis \> or = 5 years at Screening.
Lacosamide: oral tablet
Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid
Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid
Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week | 360 |
| Total | 456 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Maintenance Phase | Adverse Event | 3 | 23 |
| Maintenance Phase | Lack of Efficacy | 0 | 4 |
| Maintenance Phase | Lost to Follow-up | 2 | 7 |
| Maintenance Phase | Non compliance to study procedures | 1 | 0 |
| Maintenance Phase | Patient moving out of area | 0 | 1 |
| Maintenance Phase | Protocol Violation | 2 | 6 |
| Maintenance Phase | Withdrawal by Subject | 4 | 4 |
| Titration Phase | Adverse Event | 9 | 46 |
| Titration Phase | Lack of Efficacy | 0 | 2 |
| Titration Phase | Lost to Follow-up | 1 | 3 |
| Titration Phase | Non compliance to study procedures | 0 | 1 |
| Titration Phase | Prohibited Antiepileptic Drug change | 0 | 1 |
| Titration Phase | Protocol Violation | 3 | 7 |
| Titration Phase | Study medication not tolerated | 0 | 1 |
| Titration Phase | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | First Add-on | Later-Add-on | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 7 Participants | 11 Participants |
| Age, Categorical >=65 years | 10 Participants | 4 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 82 Participants | 349 Participants | 431 Participants |
| Age, Continuous | 37.5 years | 38.0 years | 38.0 years |
| BMI | 25.3 kilogram per m^2 | 25.5 kilogram per m^2 | 25.4 kilogram per m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 99 Participants | 123 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants | 261 Participants | 333 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 166.5 centimeter | 167.6 centimeter | 167.6 centimeter |
| Race (NIH/OMB) American Indian or Alaska Native | 11 Participants | 6 Participants | 17 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 12 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 19 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 45 Participants | 50 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 79 Participants | 278 Participants | 357 Participants |
| Sex: Female, Male Female | 53 Participants | 180 Participants | 233 Participants |
| Sex: Female, Male Male | 43 Participants | 180 Participants | 223 Participants |
| Weight | 71.8 kilogram | 73.0 kilogram | 73.0 kilogram |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 53 / 96 | 212 / 360 |
| serious Total, serious adverse events | 8 / 96 | 19 / 360 |
Outcome results
Primary
The Proportion of Subjects Who Achieved Seizure-free Status During the First 12 Weeks of the Maintenance Phase
A subject will be considered seizure-free if the subject completes the first 12 weeks of the Maintenance Phase, reports zero seizures, and has no seizure data missing for any day during the period of time. This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn.
Time frame: From Week 7 (end of Week 6) to end of Week 18
Population: The Analysis Population refers to the Completer Set (CS) which includes all subjects who were enrolled, received at least one dose of Lacosamide and completed the first 12 weeks of the Maintenance Phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| First Add-on | The Proportion of Subjects Who Achieved Seizure-free Status During the First 12 Weeks of the Maintenance Phase | 37.5 percentage of subjects |
| Later Add-on | The Proportion of Subjects Who Achieved Seizure-free Status During the First 12 Weeks of the Maintenance Phase | 14.9 percentage of subjects |