Effect of Lacosamide 200 mg Twice a Day (Bid) on Single Dose Warfarin 25 mg in Healthy Males

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of Lacosamide 200 mg twice a day (bid) on single dose pharmacokinetics (PK) and pharmacodynamics (PD) of Warfarin (25 mg) in healthy male volunteers.

Official Title
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Single-center, Open-label, Randomized 2-way Crossover Study of the Effect of Lacosamide 200 mg Twice Daily on the Single-dose Pharmacokinetics and Pharmacodynamics of Warfarin (25 mg) in Healthy Male Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Other: Lacosamide
* Other: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers 18-55 years of age BMI 18.0-30.0 kg/m2 and weight at least 50 kg Tympanic body temperature 35.0-37.5°C (95 and 99.5°F) inclusive Exclusion Criteria: Volunteer has participated or is participating in any other clinical studies of investigational drug or another Investigational Medicinal Product (IMP) within the last 3 months Volunteer is not healthy (eg, taking any drug treatments, excessive amount of alcohol, cigarettes or caffeine, having any medical or emotional/psychological problems, a drug/alcohol abuse, having abnormal safety parameters) Volunteer is taking Warfarin or Non Steroidal Anti-Inflammatory Drug (NSAID) Volunteer has history of suicide attempt Volunteer has history of coagulation abnormalities, occult blood in stool, gastrointestinal ulcer, surgery within 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single dose of Warfarin on day 3<br>Single dose of Warfarin on day 3 of a 7 day course of Lacosamide 200 mg BID | Other: Lacosamide<br>* Strength: 200 mg, Form: Tablet, Frequency: Twice daily, Duration: 9 days<br>* Other names: Vimpat;|
| Other: Single dose of Warfarin<br> | Other: Warfarin<br>* Strength: 5 mg, Form: Tablet, Frequency: 1 single dose in each period In total, during the two periods, each healthy volunteer will receive 2 single doses 3 weeks apart. Duration: single dose<br>* Other names: Coumadin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Warfarin plasma concentration versus time curve from time 0 to infinity, AUC (Warfarin) |  | Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period | 
| Area under the Warfarin plasma concentration versus time curve from time 0 to the last quantifiable level, AUC0-t(Warfarin) |  | Multiple sampling from 0 -168 hours following administration of a single warfarin dose in each treatment period | 
| Maximum Warfarin plasma concentration (Cmax) |  | Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period | 
| Maximum prothrombin time (PTmax) |  | Multiple sampling from 0 -168 hours following administration of a single warfarin dose in each treatment period | 
| Warfarin area under the prothrombin time (PT) versus time curve (PTAUC) |  | Multiple sampling from 0 -168 hours following administration of a single warfarin dose in each treatment period | 
| Warfarin maximum international normalized ratio (INRmax) |  | Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period | 
| Warfarin area under the International Normalized Ratio (INR) versus time curve (INRAUC) |  | Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lacosamide trough plasma concentration (Ctrough) |  | Morning pre dose sample on Days 3-10 or Days 24 -30 of Lacosamide BID dosing | 
| Time of maximum Warfarin plasma concentration (Tmax) |  | Multiple sampling from 0 -168 hours following administration of a single Warfarin dose | 
| Terminal half-life of Warfarin (T ½) |  | Multiple sampling from 0 -168 hours following administration of a single Warfarin dose | 
| Apparent total body clearance of Warfarin (CL /F) |  | Multiple sampling from 0 -168 hours following administration of a single Warfarin dose | 
| Apparent volume of distribution of Warfarin (V /F) |  | Multiple sampling from 0 -168 hours following administration of a single Warfarin dose | 
| First order terminal elimination rate constant of Warfarin |  | Multiple sampling from 0 -168 hours following administration of a single Warfarin dose | 
| CYP2C9 genotype |  | Single measurement on Day 1 | 
| VKORC1 genotype |  | Single measurement on Day 1 | 
| Occurrence of at Least One Treatment-emergent Adverse Event (TEAE) during the duration of the study |  | Duration of study is approximately 32 days | 
| Change from Baseline in Pulse Rate at 4 h post dose | 40-90 bpm | From pre dose to 4 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Pulse Rate at 12 h post dose | 40-90 bpm | From pre dose to 12 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Pulse Rate at 24 h post dose | 40-90 bpm | From pre dose to 24 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Pulse Rate at 4 h post dose | 40-90 bpm | From pre dose to 4 h post dose Lacosamide (LCM) administration | 
| Change from Baseline in Pulse Rate at 12 h post dose | 40-90 bpm | From pre dose to 12 h post dose LCM administration | 
| Change from Baseline in Systolic Blood Pressure at 4 h post dose |  | From pre dose to 4 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Systolic Blood Pressure at 12 h post dose |  | From pre dose to 12 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Systolic Blood Pressure at 24 h post dose |  | From pre dose to 24 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Systolic Blood Pressure at 4 h post dose |  | From pre dose to 4 h post dose LCM administration | 
| Change from Baseline in Systolic Blood Pressure at 12 h post dose | 40-90 bpm | From pre dose to 12 h post dose LCM administration | 
| Change from Baseline in Diastolic Blood Pressure at 4 h post dose |  | From pre dose to 4 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Diastolic Blood Pressure at 12 h post dose |  | From pre dose to 12 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Diastolic Blood Pressure at 24 h post dose |  | From pre dose to 24 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Diastolic Blood Pressure at 4 h post dose |  | From pre dose to 4 h post dose LCM administration | 
| Change from Baseline in Diastolic Blood Pressure at 12 h post dose | 40-90 bpm | From pre dose to 12 h post dose LCM administration | 
| Change from Baseline in Body Temperature at 4h post dose |  | From pre dose to 4 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Body Temperature at 12 h post dose |  | From pre dose to 12 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Body Temperature at 24 h post dose |  | From pre dose to 24 h post dose Warfarin administration in each treatment period | 
| Change from Baseline in Body Temperature at 4 h post dose |  | From pre dose to 4 h post dose LCM administration | 
| Change from Baseline in Body Temperature at 12 h post dose | 40-90 bpm | From pre dose to 12 h post dose LCM administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Male Healthy Volunteers