Epilepsy
Conditions
Keywords
Primary Generalized Tonic-Clonic (PGTC) Seizures, Absence Seizures, Myoclonic Seizures, Idiopathic Generalized Epilepsy (IGE)
Brief summary
The purpose is to assess the safety of Lacosamide in subjects with uncontrolled Primary Generalized Tonic-Clonic (PGTC) seizures with Idiopathic Generalized Epilepsy.
Interventions
DRUGLacosamide
Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Sponsors
UCB BIOSCIENCES, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subject has a diagnosis of uncontrolled epilepsy with primary generalized tonic-clonic (PGTC) seizures and idiopathic generalized epilepsy. Diagnosis should have been established by an electroencephalogram (EEG) with generalized spike-wave discharges within 5 years of the screening visit * Subject has ≥1 PGTC seizure within the 12 weeks prior to the screening visit * Subject has a stable dose regimen of 1 to 3 marketed antiepileptic drug(s) (AEDs) with or without additional concurrent stable Vagus Nerve Stimulation (VNS). The VNS must have been in place for at least 6 months prior to study entry with constant settings for at least 28 days prior to the screening visit and during the Baseline Phase. Benzodiazepines will be counted as an AED
Exclusion criteria
* Subject has a history of partial-onset seizures or EEG findings consistent with partial onset seizures * Subject has a history of status epilepticus within the 5-year Period prior to Visit 1 * Subject has a current or previous diagnosis of pseudoseizures, conversion disorders, or other non-epileptic ictal events * Subject has any medical or psychiatric condition * Subject has any history of alcohol or drug abuse * Subject is currently taking felbamate * Subject has ever taken vigabatrin and has no visual fields examination report available or if results of the examination are abnormal * Subject is on a ketogenic diet * Subject has a known sodium channelopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Seizure Days With Absence Seizures From the Baseline Phase to the Maintenance Phase | From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13) | During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded: * Seizure type * Seizure frequency A negative value in change of seizure days with absence seizures shows a decrease in seizure days with absence seizures. |
| Change in the Number of Seizure Days With Myoclonic Seizures From the Baseline Phase to the Maintenance Phase | From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13) | During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded: * Seizure type * Seizure frequency A negative value in change of seizure days with myoclonic seizures shows a decrease in seizure days with myoclonic seizures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Count of Generalized Spike-wave Discharges on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) | From Visit 2 (Week 4) to Visit 6 (Week 8) | Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with \> 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The general spike-wave discharges are calculated per interpretable hours. |
| Changes in Count of 3 Hertz (Hz) Spike-wave Discharges (During Waking Hours) on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) | From Visit 2 (Week 4) to Visit 6 (Week 8) | Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with \> 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The 3 Hertz (Hz) spike-wave discharges are calculated per awake hours. |
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period | From Visit 2 (Week 4) to Visit 7 (Week 13) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. |
| Number of Subjects Withdrawn From the Study Due to Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period | From Visit 2 (Week 4) to Visit 7 (Week 13) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. |
Countries
United States
Participant flow
Recruitment details
Safety Set (SS) includes all enrolled subjects who took at least 1 dose of Lacosamide (LCM).
Pre-assignment details
Participant Flow and Baseline Characteristics refer to the Safety Set (SS).
Participants by arm
| Arm | Count |
|---|---|
| Lacosamide Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week. | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Lacosamide |
|---|---|
| Age, Categorical <=18 years | 3 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants |
| Age, Continuous | 29.7 years STANDARD_DEVIATION 10.1 |
| Height | 168.08 centimeter (cm) STANDARD_DEVIATION 9.32 |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 13 Participants |
| Weight | 77.90 kilogram (kg) STANDARD_DEVIATION 19.8 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 49 |
| serious Total, serious adverse events | 1 / 49 |
Outcome results
Primary
Change in the Number of Seizure Days With Absence Seizures From the Baseline Phase to the Maintenance Phase
During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded: * Seizure type * Seizure frequency A negative value in change of seizure days with absence seizures shows a decrease in seizure days with absence seizures.
Time frame: From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)
Population: Of the 49 subjects in the Safety Set (SS), 44 are included in this analysis. Data not available for 5 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lacosamide | Change in the Number of Seizure Days With Absence Seizures From the Baseline Phase to the Maintenance Phase | -0.37 number of seizure days | Standard Deviation 4.8 |
Primary
Change in the Number of Seizure Days With Myoclonic Seizures From the Baseline Phase to the Maintenance Phase
During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded: * Seizure type * Seizure frequency A negative value in change of seizure days with myoclonic seizures shows a decrease in seizure days with myoclonic seizures.
Time frame: From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)
Population: Of the 49 subjects in the Safety Set (SS), 44 are included in this analysis. Data not available for 5 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lacosamide | Change in the Number of Seizure Days With Myoclonic Seizures From the Baseline Phase to the Maintenance Phase | -2.19 number of seizure days | Standard Deviation 5.8 |
Secondary
Changes in Count of 3 Hertz (Hz) Spike-wave Discharges (During Waking Hours) on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase)
Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with \> 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The 3 Hertz (Hz) spike-wave discharges are calculated per awake hours.
Time frame: From Visit 2 (Week 4) to Visit 6 (Week 8)
Population: Of the 49 subjects in the Safety Set (SS), 40 subjects are included in this analysis. Data not available for 9 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lacosamide | Changes in Count of 3 Hertz (Hz) Spike-wave Discharges (During Waking Hours) on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) | 0.13 1/hour | Standard Deviation 2.17 |
Secondary
Changes in Count of Generalized Spike-wave Discharges on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase)
Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with \> 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The general spike-wave discharges are calculated per interpretable hours.
Time frame: From Visit 2 (Week 4) to Visit 6 (Week 8)
Population: Of the 49 subjects in the Safety Set (SS), 40 subjects are included in this analysis. Data not available for 9 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lacosamide | Changes in Count of Generalized Spike-wave Discharges on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) | -3.47 1/hour | Standard Deviation 55.85 |
Secondary
Number of Subjects Withdrawn From the Study Due to Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
Time frame: From Visit 2 (Week 4) to Visit 7 (Week 13)
Population: All 49 subjects in the Safety Set (SS) are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lacosamide | Number of Subjects Withdrawn From the Study Due to Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period | 5 participants |
Secondary
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
Time frame: From Visit 2 (Week 4) to Visit 7 (Week 13)
Population: All 49 subjects in the Safety Set (SS) are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lacosamide | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period | 43 participants |