Epilepsy
Conditions
Keywords
Epilepsy, antiepileptic drug, polytherapy
Brief summary
This is a study to determine whether a combination of low dose lacosamide and levetiracetam is more effective than high dose levetiracetam in patients who have failed low dose levetiracetam.
Interventions
DRUGlacosamide
Lacosamide maximum of 200 mg/day, to be titrated as follows: * Week 1: 50 mg twice a day * Beginning Week 2: 100 mg twice a day.
DRUGlevetiracetam
Low dose ≤1500 mg/day, High dose \>1500 mg/day
Sponsors
Brigham and Women's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults age 18 or older 2. Determined to have had at least two partial seizures by an epilepsy specialist, or to have had a single partial seizure with clinical and/or laboratory evidence of a high seizure recurrence risk 3. Monotherapy on levetiracetam less than or equal to 1500 mg/day for at least two weeks 4. Breakthrough seizure while on stable dose (\>5 days) of levetiracetam monotherapy regimen, not due to provocative factors (e.g. hypoglycemia, head trauma, missed medications)
Exclusion criteria
1. Clinical suspicion of nonepileptic psychogenic seizures or idiopathic generalized epilepsy 2. Pregnant, child-bearing age not using contraception, or breast feeding 3. Medical contraindication to adding lacosamide 4. History of antiepileptic drug (AED) polytherapy 5. Presence of a vagus nerve stimulator 6. Creatinine clearance of less than 50 mL/min 7. Blood pressure instability: pulse \<50 or \>100, systolic blood pressure (SBP) \<50 or \>180, clinically significant electrocardiogram (EKG) abnormality 8. History of significant drug rash or anaphylactic reaction with antiepileptic drug 9. Patients with progressive lesions (e.g. brain tumors)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Six Month Seizure Freedom | 6 Months | Seizure freedom is defined as having no seizures and was evaluated in the 6 month period after receiving the drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Seizure-Free Days | 6 Months | — |
| Time to First Seizure After Therapeutic Dose is Reached | 6 Months | Time in days until the first seizure after the therapeutic dose is reached occurs. |
| Retention Rate | 6 Months | Retention rate is defined as the percentage of participants who remained on the study drug after study completion. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAE) | 6 Months | An Adverse Event (AE) is defined as any untoward medical occurrence (side effect) in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event that occurs after receiving the drug. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJong Woo Lee, MD, PhD
Brigham and Women's Hospital
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lacosamide + Low-Dose Levetiracetam Participants received lacosamide 50 mg twice a day for one week followed by 100 mg twice daily added to low dose levetiracetam ≤1500 mg/day (polytherapy) for 6 months in patients with breakthrough seizures on low-dose levetiracetam. | 20 |
| Control Group (High-Dose Levetiracetam) Historical chart review of patients whose dose of levetiracetam was raised to high dose levetiracetam \>1500 mg/day (monotherapy) after a breakthrough seizure. No intervention was administered in the study. | 36 |
| Total | 56 |
Baseline characteristics
| Characteristic | Lacosamide + Low-Dose Levetiracetam | Control Group (High-Dose Levetiracetam) | Total |
|---|---|---|---|
| Age, Continuous | 42.9 years STANDARD_DEVIATION 17.5 | 43.7 years STANDARD_DEVIATION 19.8 | 43.4 years STANDARD_DEVIATION 18.8 |
| Region of Enrollment United States | 20 Participants | 36 Participants | 56 Participants |
| Sex: Female, Male Female | 13 Participants | 17 Participants | 30 Participants |
| Sex: Female, Male Male | 7 Participants | 19 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 11 / 18 | 26 / 36 |
| serious Total, serious adverse events | 0 / 18 | 0 / 36 |
Outcome results
Primary
Percentage of Participants Achieving Six Month Seizure Freedom
Seizure freedom is defined as having no seizures and was evaluated in the 6 month period after receiving the drug.
Time frame: 6 Months
Population: All eligible participants. One participant in the Lacosamide + Low-Dose Levetiracetam arm did not receive study drug and is not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lacosamide + Low-Dose Levetiracetam | Percentage of Participants Achieving Six Month Seizure Freedom | 47.4 percentage of participants |
| Control Group (High-Dose Levetiracetam) | Percentage of Participants Achieving Six Month Seizure Freedom | 41.7 percentage of participants |
p-value: 0.4995% CI: [0.35, 1.65]Chi-squared
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAE)
An Adverse Event (AE) is defined as any untoward medical occurrence (side effect) in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event that occurs after receiving the drug.
Time frame: 6 Months
Population: All eligible participants. One participant in the Lacosamide + Low-Dose Levetiracetam arm did not receive study drug and is not included. One participant never confirmed taking the study medication, never followed up, and was not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lacosamide + Low-Dose Levetiracetam | Number of Participants With Treatment-Emergent Adverse Events (TEAE) | 11 Participants |
| Control Group (High-Dose Levetiracetam) | Number of Participants With Treatment-Emergent Adverse Events (TEAE) | 26 Participants |
Secondary
Number of Seizure-Free Days
Time frame: 6 Months
Population: All eligible participants. One participant in the Lacosamide + Low-Dose Levetiracetam arm did not receive study drug and is not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lacosamide + Low-Dose Levetiracetam | Number of Seizure-Free Days | 118.11 days | Standard Deviation 68.59 |
| Control Group (High-Dose Levetiracetam) | Number of Seizure-Free Days | 114.0 days | Standard Deviation 65.06 |
Secondary
Retention Rate
Retention rate is defined as the percentage of participants who remained on the study drug after study completion.
Time frame: 6 Months
Population: All eligible participants. One participant in the Lacosamide + Low-Dose Levetiracetam arm did not receive study drug and is not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lacosamide + Low-Dose Levetiracetam | Retention Rate | 89 percentage of participants |
| Control Group (High-Dose Levetiracetam) | Retention Rate | 80 percentage of participants |
Secondary
Time to First Seizure After Therapeutic Dose is Reached
Time in days until the first seizure after the therapeutic dose is reached occurs.
Time frame: 6 Months
Population: All eligible participants. One participant in the Lacosamide + Low-Dose Levetiracetam arm did not receive study drug and is not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lacosamide + Low-Dose Levetiracetam | Time to First Seizure After Therapeutic Dose is Reached | 162.0 days |
| Control Group (High-Dose Levetiracetam) | Time to First Seizure After Therapeutic Dose is Reached | 116.5 days |