AED/Statin Interaction Study

Study Overview
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Brief Summary
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This study will evaluate the amount of the cholesterol-lowering drug atorvastatin available in the bloodstream, when taken together with the anti-seizure drugs lamotrigine or phenytoin.

Official Title
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An Open-label, Two-cohort Study to Assess the Effect of Lamotrigine and Phenytoin on the Pharmacokinetics of Atorvastatin in Healthy Subjects

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: lamotrigine
* Drug: atorvastatin
* Drug: phenytoin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body weight >50kg (men) or >45kg (women) and BMI within the range 19-32 kg/m2 inclusive. No clinically significant abnormality on clinical examination Key Exclusion Criteria: History or evidence of drug or alcohol abuse or active tobacco use. Women of childbearing potential Use of prescribed or non-prescribed medications during and within 14 days of starting study medication.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lamotrigine<br>Subjects will receive 40 milligram (mg) of Atrovastatin from Days 1-7, from Days 8-56 subjects will receive Lamotrigine and Subjects will receive 300 mg/day of Lamotrigine and 40 mg/day of atorvastatin each morning on Days 57-77. | Drug: lamotrigine<br>* Lamotrigine tablets will be available in 25, 50, 100 and 200 mg dose strength.<br>Drug: atorvastatin<br>* Atorvastatin will available as 40 mg tablets.<br>|
| Active Comparator: phenytoin<br>Subjects will receive 40 mg of Atrovastatin from Days 1-7, from Days 8-28, subjects will receive 4mg/kg/day of phenytoin in the morning and will continue to take 40 mg/day of atorvastatin each morning. Subjects will receive taper dose of phenytoin from Days 29-30. | Drug: atorvastatin<br>* Atorvastatin will available as 40 mg tablets.<br>Drug: phenytoin<br>* Phenytoin will available as 100 mg capsules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steady-state Cmax and AUC (0-t) of atorvastatin | Steady-state Cmax and AUC (0-t) of atorvastatin when dosed to steady-state. | Pre-dose,0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 20 and 24 hrs post dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of lamotrigine or phenytoin on the pharmacokinetics of 2-OH atorvastatin and 4-OH atorvastatin | Steady state Tmax, Cmax and AUC of 2-OH atorvastatin and 4-OH atorvastatin in the presence and absence of LTG XR or phenytoin. | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 20 and 24 hrs post dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug interaction, pharmacokinetics, healthy volunteers