AED/Statin Interaction Study

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00627575

Collaborator

(none)

119

Enrollment

Location

Arms

7.3

Actual Duration (Months)

16.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: lamotrigine Drug: atorvastatin Drug: phenytoin	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

119 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 4, 2008

Actual Primary Completion Date :

Sep 12, 2008

Actual Study Completion Date :

Sep 12, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lamotrigine 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 Lamotrigine tablets will be available in 25, 50, 100 and 200 mg dose strength. Drug: atorvastatin Atorvastatin will available as 40 mg tablets.
Active Comparator: phenytoin 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 Atorvastatin will available as 40 mg tablets. Drug: phenytoin Phenytoin will available as 100 mg capsules.

Arm

Intervention/Treatment

Active Comparator: Lamotrigine

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

Lamotrigine tablets will be available in 25, 50, 100 and 200 mg dose strength.

Drug: atorvastatin

Atorvastatin will available as 40 mg tablets.

Active Comparator: phenytoin

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

Atorvastatin will available as 40 mg tablets.

Drug: phenytoin

Phenytoin will available as 100 mg capsules.

Outcome Measures

Primary Outcome Measures

Steady-state Cmax and AUC (0-t) of atorvastatin [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.]
Steady-state Cmax and AUC (0-t) of atorvastatin when dosed to steady-state.

Secondary Outcome Measures

To assess the effect of lamotrigine or phenytoin on the pharmacokinetics of 2-OH atorvastatin and 4-OH atorvastatin [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.]
Steady state Tmax, Cmax and AUC of 2-OH atorvastatin and 4-OH atorvastatin in the presence and absence of LTG XR or phenytoin.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.