BEEP Follow Up: Evaluation of Repeatability of Lamotrigine Pharmacokinetics in Epileptic Patients

Phase 4

Completed

Conditions: Epilepsy

Interventions: Drug: lamotrigine (generic Teva)
Drug: lamotrigine (brand Lamictal)

Registration Number: NCT02404168

Lead Sponsor: University of Maryland, Baltimore

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 4

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
lamotrigine generic tablet2	lamotrigine (generic Teva)	lamotrigine tablet Teva
lamotrigine brand tablet1	lamotrigine (brand Lamictal)	lamotrigine tablet Lamictal
lamotrigine generic tablet1	lamotrigine (generic Teva)	lamotrigine tablet Teva
lamotrigine brand tablet2	lamotrigine (brand Lamictal)	lamotrigine tablet Lamictal

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures