Epilepsy
Conditions
Brief summary
The prior BEEP study involved patients being switched between brand and generic in a very structured manner. Other secondary comparisons were also made (i.e. any differences in adverse effects and seizure control). Some subjects were more disparate than other, in terms of generic being similar to brand. In this follow up study, BEEP subjects that showed disparate results will be tested again to assess reproducibility of disparate results.
Detailed description
This is an double-blind, multiple-dose, full replicate design, pharmacokinetic study of lamotrigine in enriched patients with epilepsy who previously participated in HP-00048923. LAMICTAL 100mg tablets and the most commonly used generic lamotrigine 100mg tablet (from Teva) will be compared pharmacokinetically.
Interventions
DRUGlamotrigine (brand Lamictal)
an anti-epileptic drug (brand)
DRUGlamotrigine (generic Teva)
an anti-epileptic drug (brand)
Sponsors
University of Maryland, Baltimore
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
* Subject is able to provide informed consent and was enrolled in previous BEEP study. * Subject is male or female between 18 and 76 years of age inclusive. * Subject has a diagnosis of epilepsy with simple partial seizures and/or complex partial seizures, with or without secondary generalization or primary generalized seizures * Subject has been maintained on a stable dose regimen of anti-epileptic drugs (AEDs), including lamotrigine at 200mg, 400mg, or 600mg total daily dosage divided BID for at least 8 weeks prior to Visit 1 and during the screening period * Subject is willing to be switched between brand and generic lamotrigine * Subject is an acceptable candidate for venipuncture * Subject is willing to stop all OTC medications for 24 hours prior to and during 12 hour study visits
Exclusion criteria
* Subject is currently participating or has participated within the last 2 months in any trial of an investigational drug or experimental device * Subject has a history of status epilepticus within the 12 month period prior to Visit 1. * Subject has any medical 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 * Subject has any psychiatric condition, 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 or confound the interpretation of the trial data * Subject has known hypersensitivity to lamotrigine * Subject has a medical condition that impacts drug absorption (e.g. gastric bypass surgery), including routine use (i.e. daily or weekly) use of acid blockers, antacids, anti-diarrhea, stimulants, appetite suppressants, or anti nausea medication or other drugs that modulate GI function * Subject has any history of alcohol or drug abuse within the previous two years * Subject has acute or subacutely progressive CNS disease * Subject has moderate or severe liver impairment as assessed by alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels ≥5 times the upper limit of normal (ULN). * Subject has moderate or severe renal impairment as assessed by creatinine clearance lower than 50mL/min, using the Cockcroft-Gault formula * 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 * Female subject is pregnant or nursing * Female subject is using hormonal contraceptive precautions including progesterone-coated IUD * Subjects is using hormonal replacement therapy * Subject is unwilling or unable to maintain their approximate daily smoking use during the study * Subject is using rifampin or other non-AED that strongly modulates lamotrigine levels * addition to lamotrigine and/or vagus nerve stimulation and/or intermittent benzodiazepine use (e.g. lorazepam, diazepam, clonazepam), subject is taking more than two concomitant AEDs * Subject is not willing or able to be adherent to study protocol (e.g. dosing of lamotrigine and any interacting comedication).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC | 0-12hr | pharmacokinetic exposure (ng\*hr/ml). Pharmacokinetic (PK) blood levels will be drawn at the schedule times: immediately prior to lamotrigine administration, then after drug administration at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hr. |
| Cmax | 0-12hr | pharmacokinetic rate (ng/ml). Pharmacokinetic (PK) blood levels will be drawn at the schedule times: immediately prior to lamotrigine administration, then after drug administration at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hr. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lamotrigine Tablet Sequence: generic first, then brand, then brand, and then generic | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Lamotrigine Tablet |
|---|---|
| Age, Continuous | 48 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 1 / 4 | 3 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 |
Outcome results
Primary
AUC
pharmacokinetic exposure (ng\*hr/ml). Pharmacokinetic (PK) blood levels will be drawn at the schedule times: immediately prior to lamotrigine administration, then after drug administration at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hr.
Time frame: 0-12hr
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Comparator: Lamotrigine Brand | AUC | 79640 ng*hr/ml | Standard Error 11442 |
| Experimental: Lamotrigine Generic | AUC | 81653 ng*hr/ml | Standard Error 11991 |
Primary
Cmax
pharmacokinetic rate (ng/ml). Pharmacokinetic (PK) blood levels will be drawn at the schedule times: immediately prior to lamotrigine administration, then after drug administration at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hr.
Time frame: 0-12hr
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Comparator: Lamotrigine Brand | Cmax | 8836 ng/ml | Standard Error 1245 |
| Experimental: Lamotrigine Generic | Cmax | 9024 ng/ml | Standard Error 1203 |