Epilepsy
Conditions
Keywords
Generic brittle, Anti-epileptic drug, Bioequivalence
Brief summary
Some epilepsy patients are described as GB when they have worsened seizures or side effects related to switching between brand name and generic, or between generic antiepileptic drug (AED) products. In concert with Aim 1 (protocol BEEP2a), this study will uncover possible reasons for patient problems with the drug switching. Factors that will be studied in GB epilepsy patients include physiologic, psychological, and genetic factors, including in this protocol whether brand and generic AEDs are pharmacokinetically similar in GB individuals.
Detailed description
This pilot study is exploratory research to characterize the generic brittle (GB) patient and to identify major causes for generic brittleness in epilepsy patients who are sensitive to antiepileptic drug (AED) formulation changes. The primary aim of this BEEP2b study is to perform individual pharmacokinetic (PK) similarity testing of brand and generic AEDs in probably GB patients (N=12),who were selected on the basis of having GB-defining factors from the BEEP2a study, in order to confirm whether these factors are predictive of a generic brittle response to product switching. The study design involves a randomized, double-blind, multiple-dose, complete four-way replicate crossover design in which one brand and one generic will be compared in each patient from the patient's own AED regimen. Associated adverse events (i.e. seizures and side effects) will also be assessed. Bioequivalence (BE) will not be assessed. Rather, about nine AEDs are expected to be collectively evaluated. Generic brittleness anticipates that, for individual subjects, brand and generic may be the same or different, depending upon the underlying basis for generic brittleness. This exploratory research is focused on understanding individual patient attributes that contribute to GB, and is not focused on either product development or comparison of specific products.
Interventions
DRUGOxcarbazepine (brand name vs generic drugs)
This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
DRUGDivalproex Sodium (brand name vs generic drugs)
This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
DRUGCarbamazepine (brand name vs generic drugs)
This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
DRUGLamotrigine (brand name vs generic drugs)
This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
DRUGlevetiracetam (brand name vs generic drugs)
This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
DRUGTopiramate (brand name vs generic drugs)
This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
DRUGZonisamide (brand name vs generic drugs)
This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
DRUGPhenytoin sodium (brand name vs generic drugs)
This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
Sponsors
University of Maryland, Baltimore
Food and Drug Administration (FDA)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
1. Subject previously completed BEEP2a study, found to be probably GB, and able to provide informed consent or subject's legally authorized representative is able to provide informed consent. 2. Subject is male or female between 18 and 76 years of age inclusive. 3. Subject has a diagnosis of epilepsy including focal or primary generalized epilepsy. 4. Subject is taking at least one study antiepileptic drug for the treatment of epilepsy. 5. Subject is an acceptable candidate for venipuncture. 6. Subject is willing to be switched between brand and generic drug. 7. Subject is willing to stop all non-routine OTC medications for 24 hours prior to and during pharmacokinetic study visits. 8. Subject is willing to maintain stable doses of all other AEDs, including Vagus Nerve Stimulation parameters for the duration of the study.
Exclusion criteria
1. Subject has any medical condition, including a progressive neurological condition, which in the opinion of the investigator, could jeopardize the subject's health or would compromise the subject's ability to participate in the trial. 2. Subject has a history of alcohol or drug abuse, which in the opinion of the investigator, could jeopardize the subject's health or would compromise the subject's ability to participate in this trial. 3. Subject has a history of previous or current significant psychiatric disorder that would interfere with conduct of the study. 4. Subject is pregnant or lactating. 5. Subject has severe liver impairment as assessed by alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels ≥10 times the upper limit of normal (ULN). 6. Subject has severe renal impairment as assessed by creatinine clearance lower than 30mL/min, using the Cockcroft-Gault formula. 7. Female subjects of childbearing potential will not be eligible to participate who are unwilling or unable to use a medically acceptable method of contraception throughout the entire study period and for one week after the study is completed. Medically acceptable methods of contraception that may be used by the subject and/or her partner are: condom with spermicide, diaphragm with spermicide, IUD without progesterone, vaginal spermicidal suppository, surgical sterilization of their partner(s) or abstinence. 8. Subject is not willing or able to be adherent to study protocol (e.g. study medication dosing and any interacting comedication).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean AUC0-last_ss (Test vs. Reference) | For all study drugs, time points are: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hr postdose. For twice-a-day regimen, additional points are:8, 10, and 12 hr postdose. For once-a-day drugs, additional times are:8, 10, 12, 16, and 24 hr postdose. | Average AUC (area under the drug plasma curve. |
| Mean Cmax_ss (Test vs. Reference) | For all study drugs, time points are: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hr postdose. For twice-a-day regimen, additional points are:8, 10, and 12 hr postdose. For once-a-day drugs, additional times are:8, 10, 12, 16, and 24 hr postdose. | Average maximum drug plasma concentration; |
| Mean Cmin_ss (Test vs. Reference) | For all study drugs, time points are: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hr postdose. For twice-a-day regimen, additional points are:8, 10, and 12 hr postdose. For once-a-day drugs, additional times are:8, 10, 12, 16, and 24 hr postdose. | Average minimum drug plasma concentration (Cmin); |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | Through the approximately 2 week period when the treatment is given. | summed for each anti-epileptic drug from when taking brand and generic. |
| Number of Seizures Reported | Through the approximately 2 week period when the treatment is given. | Number of seizures reported in all groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topiramate Tablet Group All subjects who received the Topiramate Tablet. | 5 |
| Lamotrigine IR Tablet Group All subjects who received the Lamotrigine IR Tablet. | 1 |
| Lamotrigine ER Tablet Group All subjects who received the Lamotrigine ER Tablet. | 3 |
| Levetiracetam IR Tablet Group All subjects who received the Levetiracetam IR Tablet. | 3 |
| Levetiracetam ER Tablet Group All subjects who received the Levetiracetam ER Tablet. | 2 |
| Carbamazepine ER Capsule All subjects who received the Carbamazepine ER Capsule. | 2 |
| Carbamazepine ER Tablet All subjects who received the Carbamazepine ER Tablet. | 1 |
| Zonisamide Capsule Group All subjects who received the Zonisamide Capsule. | 1 |
| Valproic Acid ER Tablet Group All subjects who received the Valproic Acid ER Tablet. | 2 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | PI decisions | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Protocol deviation | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Lamotrigine IR Tablet Group | Lamotrigine ER Tablet Group | Topiramate Tablet Group | Levetiracetam IR Tablet Group | Levetiracetam ER Tablet Group | Carbamazepine ER Capsule | Carbamazepine ER Tablet | Zonisamide Capsule Group | Valproic Acid ER Tablet Group |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 1 Participants | 3 Participants | 5 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 1 Participants | 3 Participants | 5 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 18 Participants | 1 Participants | 1 Participants | 5 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 | 0 / 3 | 0 / 2 | 0 / 1 | 0 / 1 | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 5 / 5 | 4 / 4 | 2 / 3 | 2 / 2 | 2 / 3 | 1 / 1 | 1 / 1 | 1 / 2 |
| serious Total, serious adverse events | 0 / 5 | 0 / 3 | 0 / 3 | 0 / 2 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 2 |
Outcome results
Primary
Mean AUC0-last_ss (Test vs. Reference)
Average AUC (area under the drug plasma curve.
Time frame: For all study drugs, time points are: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hr postdose. For twice-a-day regimen, additional points are:8, 10, and 12 hr postdose. For once-a-day drugs, additional times are:8, 10, 12, 16, and 24 hr postdose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate Tablet | Mean AUC0-last_ss (Test vs. Reference) | Test Product | 92.884 micro/mL/hr | Standard Deviation 45.04955804 |
| Topiramate Tablet | Mean AUC0-last_ss (Test vs. Reference) | Reference Product | 94.456 micro/mL/hr | Standard Deviation 46.91455403 |
| Lamotrigine ER Tablet | Mean AUC0-last_ss (Test vs. Reference) | Test Product | 62.76666667 micro/mL/hr | Standard Deviation 26.51919556 |
| Lamotrigine ER Tablet | Mean AUC0-last_ss (Test vs. Reference) | Reference Product | 67.19333333 micro/mL/hr | Standard Deviation 28.83182501 |
| Levetiracetam IR Tablet | Mean AUC0-last_ss (Test vs. Reference) | Test Product | 419.97 micro/mL/hr | Standard Deviation 116.7864209 |
| Levetiracetam IR Tablet | Mean AUC0-last_ss (Test vs. Reference) | Reference Product | 445.2 micro/mL/hr | Standard Deviation 125.97458 |
| Levetiracetam ER Tablet | Mean AUC0-last_ss (Test vs. Reference) | Test Product | 260.3 micro/mL/hr | Standard Deviation 169.1399421 |
| Levetiracetam ER Tablet | Mean AUC0-last_ss (Test vs. Reference) | Reference Product | 262.305 micro/mL/hr | Standard Deviation 176.4584972 |
| Carbamazepine ER Capsule | Mean AUC0-last_ss (Test vs. Reference) | Test Product | 114.96 micro/mL/hr | Standard Deviation 0 |
| Carbamazepine ER Capsule | Mean AUC0-last_ss (Test vs. Reference) | Reference Product | 106.45 micro/mL/hr | Standard Deviation 0 |
| Carbamazepine ER Tablet | Mean AUC0-last_ss (Test vs. Reference) | Test Product | 104.6 micro/mL/hr | Standard Deviation 0 |
| Carbamazepine ER Tablet | Mean AUC0-last_ss (Test vs. Reference) | Reference Product | 115.16 micro/mL/hr | Standard Deviation 0 |
| Zonisamide Capsule | Mean AUC0-last_ss (Test vs. Reference) | Reference Product | 226.14 micro/mL/hr | Standard Deviation 0 |
| Zonisamide Capsule | Mean AUC0-last_ss (Test vs. Reference) | Test Product | 233.16 micro/mL/hr | Standard Deviation 0 |
Primary
Mean Cmax_ss (Test vs. Reference)
Average maximum drug plasma concentration;
Time frame: For all study drugs, time points are: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hr postdose. For twice-a-day regimen, additional points are:8, 10, and 12 hr postdose. For once-a-day drugs, additional times are:8, 10, 12, 16, and 24 hr postdose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate Tablet | Mean Cmax_ss (Test vs. Reference) | Test Product | 9.874 microg/mL | Standard Deviation 4.889389532 |
| Topiramate Tablet | Mean Cmax_ss (Test vs. Reference) | Reference Product | 9.646 microg/mL | Standard Deviation 4.834328288 |
| Lamotrigine ER Tablet | Mean Cmax_ss (Test vs. Reference) | Test Product | 6.24 microg/mL | Standard Deviation 2.327853088 |
| Lamotrigine ER Tablet | Mean Cmax_ss (Test vs. Reference) | Reference Product | 6.903333333 microg/mL | Standard Deviation 2.460819647 |
| Levetiracetam IR Tablet | Mean Cmax_ss (Test vs. Reference) | Test Product | 71.02333333 microg/mL | Standard Deviation 16.29206658 |
| Levetiracetam IR Tablet | Mean Cmax_ss (Test vs. Reference) | Reference Product | 69.29333333 microg/mL | Standard Deviation 15.89970545 |
| Levetiracetam ER Tablet | Mean Cmax_ss (Test vs. Reference) | Test Product | 31.05 microg/mL | Standard Deviation 16.64529363 |
| Levetiracetam ER Tablet | Mean Cmax_ss (Test vs. Reference) | Reference Product | 28.04 microg/mL | Standard Deviation 17.2675476 |
| Carbamazepine ER Capsule | Mean Cmax_ss (Test vs. Reference) | Test Product | 10.95 microg/mL | Standard Deviation 0 |
| Carbamazepine ER Capsule | Mean Cmax_ss (Test vs. Reference) | Reference Product | 9.91 microg/mL | Standard Deviation 0 |
| Carbamazepine ER Tablet | Mean Cmax_ss (Test vs. Reference) | Test Product | 10.00 microg/mL | Standard Deviation 0 |
| Carbamazepine ER Tablet | Mean Cmax_ss (Test vs. Reference) | Reference Product | 10.6 microg/mL | Standard Deviation 0 |
| Zonisamide Capsule | Mean Cmax_ss (Test vs. Reference) | Test Product | 12.29 microg/mL | Standard Deviation 0 |
| Zonisamide Capsule | Mean Cmax_ss (Test vs. Reference) | Reference Product | 11.68 microg/mL | Standard Deviation 0 |
Primary
Mean Cmin_ss (Test vs. Reference)
Average minimum drug plasma concentration (Cmin);
Time frame: For all study drugs, time points are: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hr postdose. For twice-a-day regimen, additional points are:8, 10, and 12 hr postdose. For once-a-day drugs, additional times are:8, 10, 12, 16, and 24 hr postdose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate Tablet | Mean Cmin_ss (Test vs. Reference) | Test Product | 6.326 microg/mL | Standard Deviation 2.990924606 |
| Topiramate Tablet | Mean Cmin_ss (Test vs. Reference) | Reference Product | 6.53 microg/mL | Standard Deviation 3.261203765 |
| Lamotrigine ER Tablet | Mean Cmin_ss (Test vs. Reference) | Test Product | 4.053333333 microg/mL | Standard Deviation 1.569214241 |
| Lamotrigine ER Tablet | Mean Cmin_ss (Test vs. Reference) | Reference Product | 4.21 microg/mL | Standard Deviation 2.343736333 |
| Levetiracetam IR Tablet | Mean Cmin_ss (Test vs. Reference) | Test Product | 15.45333333 microg/mL | Standard Deviation 4.702981324 |
| Levetiracetam IR Tablet | Mean Cmin_ss (Test vs. Reference) | Reference Product | 17.45666667 microg/mL | Standard Deviation 6.150612436 |
| Levetiracetam ER Tablet | Mean Cmin_ss (Test vs. Reference) | Test Product | 12.605 microg/mL | Standard Deviation 12.21173411 |
| Levetiracetam ER Tablet | Mean Cmin_ss (Test vs. Reference) | Reference Product | 14.395 microg/mL | Standard Deviation 12.40972401 |
| Carbamazepine ER Capsule | Mean Cmin_ss (Test vs. Reference) | Test Product | 8.56 microg/mL | Standard Deviation 0 |
| Carbamazepine ER Capsule | Mean Cmin_ss (Test vs. Reference) | Reference Product | 7.66 microg/mL | Standard Deviation 0 |
| Carbamazepine ER Tablet | Mean Cmin_ss (Test vs. Reference) | Test Product | 7.37 microg/mL | Standard Deviation 0 |
| Carbamazepine ER Tablet | Mean Cmin_ss (Test vs. Reference) | Reference Product | 7.97 microg/mL | Standard Deviation 0 |
| Zonisamide Capsule | Mean Cmin_ss (Test vs. Reference) | Test Product | 8.46 microg/mL | Standard Deviation 0 |
| Zonisamide Capsule | Mean Cmin_ss (Test vs. Reference) | Reference Product | 8.34 microg/mL | Standard Deviation 0 |
Secondary
Number of Adverse Events
summed for each anti-epileptic drug from when taking brand and generic.
Time frame: Through the approximately 2 week period when the treatment is given.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Topiramate Tablet | Number of Adverse Events | 29 events |
| Lamotrigine ER Tablet | Number of Adverse Events | 9 events |
| Levetiracetam IR Tablet | Number of Adverse Events | 17 events |
| Levetiracetam ER Tablet | Number of Adverse Events | 4 events |
| Carbamazepine ER Capsule | Number of Adverse Events | 15 events |
| Carbamazepine ER Tablet | Number of Adverse Events | 6 events |
| Zonisamide Capsule | Number of Adverse Events | 10 events |
| Valproic Acid | Number of Adverse Events | 10 events |
Secondary
Number of Seizures Reported
Number of seizures reported in all groups
Time frame: Through the approximately 2 week period when the treatment is given.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topiramate Tablet | Number of Seizures Reported | Reference Product | 9 Number of Seizures |
| Topiramate Tablet | Number of Seizures Reported | Test (Generic) | 5 Number of Seizures |
| Lamotrigine ER Tablet | Number of Seizures Reported | Reference Product | 0 Number of Seizures |
| Lamotrigine ER Tablet | Number of Seizures Reported | Test (Generic) | 0 Number of Seizures |
| Levetiracetam IR Tablet | Number of Seizures Reported | Reference Product | 44 Number of Seizures |
| Levetiracetam IR Tablet | Number of Seizures Reported | Test (Generic) | 25 Number of Seizures |
| Levetiracetam ER Tablet | Number of Seizures Reported | Reference Product | 16 Number of Seizures |
| Levetiracetam ER Tablet | Number of Seizures Reported | Test (Generic) | 5 Number of Seizures |
| Carbamazepine ER Capsule | Number of Seizures Reported | Reference Product | 42 Number of Seizures |
| Carbamazepine ER Capsule | Number of Seizures Reported | Test (Generic) | 72 Number of Seizures |
| Carbamazepine ER Tablet | Number of Seizures Reported | Test (Generic) | 1 Number of Seizures |
| Carbamazepine ER Tablet | Number of Seizures Reported | Reference Product | 3 Number of Seizures |
| Zonisamide Capsule | Number of Seizures Reported | Test (Generic) | 0 Number of Seizures |
| Zonisamide Capsule | Number of Seizures Reported | Reference Product | 0 Number of Seizures |
| Valproic Acid | Number of Seizures Reported | Reference Product | 0 Number of Seizures |
| Valproic Acid | Number of Seizures Reported | Test (Generic) | 0 Number of Seizures |
| Valproic Acid ER Tablet Group | Number of Seizures Reported | Reference Product | 12 Number of Seizures |
| Valproic Acid ER Tablet Group | Number of Seizures Reported | Test (Generic) | 0 Number of Seizures |