A Bioavailability Crossover Study of Two Formulations of Lamotrigine Extended Release Tablets in Healthy Subjects
Condition: Healthy
Intervention: Lamotrigine Extended Release
Intervention description: Lamotrigine Extended Release (generic) and Lamictal XR (brand).
Intervention MeSH terms: Lamotrigine
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bioequivalence; Lamotrigine Extended Release; Generic; Pharmacokinetic

Summary:

      The objective of this study is to determine bioequivalence between two different formulations
      of lamotrigine extended release tablets (one reference product and one generic product) in a
      healthy adult population, following a single oral dose under fed conditions.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy male or female subjects ≥18 to ≤50 years of age

          2. Subject is willing and able to provide informed consent

          3. Body mass index (BMI) greater than or equal to 18.00 kg/m2 and below 30.00 kg/m2 at
             screening

          4. Body weight greater than or equal to 50 kg at screening

          5. Subject is a non-smoker and has not used any nicotine containing products within 6
             months prior to screening

          6. Subjects who are considered generally healthy upon completion of medical history,
             physical examination, vital signs, screening laboratory results and screening ECG in
             the opinion of the Investigator

          7. Subjects who are willing and able to comply with the visit schedule, laboratory tests,
             pharmacokinetic sampling schedule and other study procedures

          8. Subjects who are willing and able to maintain their eligibility throughout the study.

          9. A female study subject must meet one of the following criteria:

               -  If of childbearing potential - agrees to use one of the accepted contraceptive
                  regimens from at least 30 days prior to the first administration of the study
                  medication, during the study, and for at least 30 days after the last dose of the
                  study medication. An acceptable method of contraception includes one of the
                  following:

                    -  Abstinence from heterosexual intercourse

                    -  Progestogen-containing hormonal contraceptives (birth control pills,
                       injectable/implant/insertable hormonal birth control products, transdermal
                       patch)

                    -  Intrauterine device (without hormones)

                    -  Condom with spermicide

               -  If a female of non-childbearing potential - should be surgically sterile (i.e.
                  has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation)
                  or in a menopausal state (at least 1 year without menses), as confirmed by FSH
                  levels (post menopausal must be confirmed by the subject having a serum follicle
                  stimulating hormone greater than 40mIU/ml at screening). Females of
                  non-childbearing potential must present a proof of partial or total hysterectomy;
                  if such proof is not available, the female will be considered to be of
                  childbearing potential.

         10. A male study subject must agree to use one of the accepted contraceptive regimens
             during the study and for at least 90 days after the last dose of the study medication;

               -  Abstinence from heterosexual intercourse

               -  Female partner with hormonal contraceptives (birth control pills,
                  injectable/implant/insertable hormonal birth control products, transdermal patch)

               -  Female partner with intrauterine device (with or without hormones)

               -  Female partner with condom with spermicide used by male study subject

               -  Female partner of non-childbearing potential

               -  Male sterilization with absence of sperm in the post vasectomy ejaculate

         11. A male study subject must agree not to donate sperm during the study and for at least
             90 days after the last dose of the study medication

        Exclusion Criteria:

          1. Females who are pregnant or are breastfeeding

          2. Females who are using any estrogen-containing hormonal contraceptives

          3. History of known clinically significant drug allergies or reactions to lamotrigine, or
             any related products (including excipients of the formulations) as well as severe
             hypersensitivity reactions (like angioedema) to any drugs in the opinion of the
             Investigator

          4. Clinically significant history or evidence of gastrointestinal, hepatic, renal,
             endocrine, pulmonary, neurological, psychiatric, cardiovascular, hematologic,
             dermatologic, immunologic disease or any other condition known to interfere with the
             absorption, distribution, metabolism or distribution of drugs that in the opinion of
             the Investigator would jeopardize the safety of the subject or impact validity of
             study results

          5. Presence of observed abnormality (evidenced from physical examination, ECG, vital
             signs, or laboratory evaluation) that would be clinically significant in the opinion
             of the Investigator

          6. History of regular alcohol consumption exceeding 7 drinks per week for females and 14
             drinks per week for males within 6 months of screening

          7. Has current or recent history (within the past year) of alcohol or drug abuse or
             dependence

          8. Any clinically significant illness in the previous 30 days prior to screening

          9. Use of any enzyme-modifying drugs, including strong inhibitors of CYP enzymes (such as
             cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole,
             ketoconazole, diltiazem, and HIV antivirals) and strong inducers of CYP enzymes (such
             as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, St John's Wort)
             in the previous 30 days prior to screening

         10. Known presence of rare hereditary problems of galactose and /or lactose intolerance or
             glucose-galactose malabsorption

         11. Unusual dietary habits (e.g., vegan, Atkins), dietary restrictions, and/or food
             allergies.

         12. Any planned surgery from the screening visit until the end of the study

         13. Positive urine screen for alcohol, cotinine and/or drugs of abuse at screening and at
             each admission of each treatment period

         14. Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg)
             or Hepatitis C Antibody (HCVAb)

         15. Albumin values less than 4 g/dL at screening

         16. Triglyceride values greater than 200 mg/dL at screening

         17. Treatment with any investigational drug 30 days prior to screening

         18. Participation in other clinical studies within 30 days prior to screening

         19. Blood donation (excluding plasma donation) of approximately 500 mL within 56 days
             prior to screening

         20. Subject is unlikely to comply with the study protocol or, in the opinion of the
             Investigator, would not be a suitable candidate for participation in the trial