Lamotrigine Bioequivalence
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: Brand lamotrigine; Generic lamotrigine
Intervention description: Brand lamotrigine tablet 100mg tablets (1-3 either once or twice a day) for two weeks; Generic lamotrigine tablet 100mg tablets (1-3 either once or twice a day) for two weeks
Intervention MeSH terms: Lamotrigine; Anticonvulsants
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: bioequivalence; lamotrigine; epilepsy

Summary:

      In this study, brand name lamotrigine (LAMICTAL) and generic lamotrigine will be compared in
      patients with epilepsy. Both the brand name and generic lamotrigine are approved by the Food
      and Drug Administration (FDA) and are commonly used to treat epilepsy. Some physicians and
      patients with epilepsy have believed that brand and generic lamotrigine have had clinically
      significant differences in efficacy and tolerability. The brand name and generic tablets have
      been shown to be the same when blood levels were measured in healthy volunteers without
      epilepsy, but these drugs have not yet been compared in patients with epilepsy. This study
      will do this comparison, by switching patients between brand and generic in a very structured
      manner, and seeing if the drugs are the same, primarily in terms of blood levels. Other
      comparisons will also be made secondarily, looking for any differences in adverse effects and
      seizure control.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject is able to provide informed consent.

          -  Subject is male or female between 18 and 65 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 had a history of at least one seizure and/or AED related adverse event
             with AED changes; or had at least one seizure and/or AED related adverse event over
             the 12 months prior to Visit 1.

          -  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 28 days prior to Visit 1. Additionally, subject must be taking lamotrigine for 8
             weeks prior to Visit 1.

          -  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.

          -  In 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).