Bioequivalence and Food Effect of 250mg of Lamotrigine XR

Study Overview
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Brief Summary
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This study intends to demonstrate bioequivalence and lack of food effect on 250mg lamotrigine XR in healthy male and female volunteers

Official Title
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A Pivotal, Single-Dose, Randomised, Parallel-Group, Open-Label Study to Demonstrate Bioequivalence of 250mg Lamotrigine XR Relative to 200mg + 50mg Lamotrigine XR and to Demonstrate Lack of Food Effect on 250mg Lamotrigine XR in Healthy Male and Female Volunteers

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Lamotrigine tablet
* Drug: Lamotrigine caplet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged from 19 to 55 years, inclusive. Body weight >50 kg (males) or >45 kg (females) and BMI within the range 19 - 32 kg/m2 inclusive. Healthy as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, vital signs and ECG. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures Female subjects of non-child bearing potential will be eligible to participate if they meet the following criteria: Post-menopausal females defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However if indicated this should be confirmed by oestradiol and FSH levels consistent with menopause (according to local laboratory ranges). Pre-menopausal females with a documented (medical report verification) hysterectomy and/or bilateral oophorectomy, the latter only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. Female subjects of child bearing potential will be eligible to participate if they comply with the contraception requirements. A negative pre-study Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, and HIV antibody result at screening. A negative pre-study urine drug screen. A negative screen for alcohol (urine, blood or breath test). Signed and dated written informed consent prior to admission to the study. Exclusion Criteria: Female subjects of childbearing potential will not be eligible to participate who are unwilling or unable to use an appropriate method of contraception as outlined in the inclusion criteria from at least the commencement of their last normal period prior to the first dose of study medication; and to continue until the first normal period (defined as normal for the woman, both in terms of duration and quantity of menses) after treatment or 5 half lives of the study medication, whichever is the longest . Female subject is pregnant (positive serum human chorionic gonadotrophin (hCG) test at screening) or lactating. Female subjects using hormonal contraceptive precautions including progesterone-coated IUD. Female subjects using oestrogen-containing hormone replacement therapy. Subjects who have received lamotrigine previously (subjects who received placebo in a previous study will be allowed) History or evidence of drug or alcohol abuse within 12 months of study start. QTc >450msec for women and QTc >430 msec for men on the screening 12-lead ECG. Current smokers of 10 or more cigarettes per day. History of regular alcohol consumption averaging >7 drinks/week for women or >14 drinks/week for men within 6 months of screening. One drink is equivalent to 12 g alcohol = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits. Has received prescribed or non-prescribed medication (including vitamins and herbal remedies) within 14 days prior to the dosing day, which in the opinion of the Principal/Co-Investigator, may interfere with the study procedures or compromise safety. History of gastro-intestinal, hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. History of clinically relevant skin rashes that, in the opinion of the investigator, might interfere with the conduct of the study. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication. History of allergic, anaphylactic, hypersensitivity or idiosyncratic reaction(s) to lamotrigine or drugs of a similar type.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects receiving regimen A<br>Eligible subjects will receive regimen A containing lamotrigine extended release tablet of 200 milligrams plus 50 milligrams in fasted state | Drug: Lamotrigine tablet<br>* Lamotrigine extended release single dose tablet will be available with dosing strengths of 200 milligrams and 50 milligrams intended to be administered orally in fasted state. It will be a round standard convex shape tablet.<br>|
| Experimental: Subjects receiving regimen B<br>Eligible subjects will receive regimen B containing lamotrigine extended release caplet of 250 milligrams in fasted state. | Drug: Lamotrigine caplet<br>* Lamotrigine extended release single dose caplet will be available with dosing strength of 200 milligrams and 50 milligrams intended to be administered orally in fasted and fed state.<br>|
| Experimental: Subjects receiving regimen C<br>Eligible subjects will receive regimen C containing lamotrigine extended release caplet of 250 milligrams in fed state. | Drug: Lamotrigine caplet<br>* Lamotrigine extended release single dose caplet will be available with dosing strength of 200 milligrams and 50 milligrams intended to be administered orally in fasted and fed state.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics ie Serum lamotrigine Cmax and AUC(0-inf) |  | Pre-dose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 36, 48, 72, 96, 120 and 144 hours Post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK (AUC (0-t), tmax and t1/2 ) |  | Pre-dose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 36, 48, 72, 96, 120 and 144 hours Post-dose | 
| Adverse events, changes in biochemistry, haematology, urinalysis parameters, electrocardiogram parameters, blood pressure and heart rate |  | Up to day 21 | 
| Serum lamotrigine AUC (0-t), tmax and t1/2 |  | Pre-dose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 36, 48, 72, 96, 120 and 144 hours Post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteers, Bioequivalence, Food Effects