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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Other: Lacosamide; Other: Warfarin

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Zuidlaren, Netherlands
    • 001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single dose of Warfarin on day 3; Single dose of Warfarin on day 3 of a 7 day course of Lacosamide 200 mg BID	Other: Lacosamide; Strength: 200 mg, Form: Tablet, Frequency: Twice daily, Duration: 9 days; Other Names: Vimpat
Other: Single dose of Warfarin	Other: Warfarin; 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; Other Names: Coumadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: UCB Pharma
• Investigators: Study Director: UCB Clinical Trial Call Center, 1 877 822 9493

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: January 31, 2012
• First Submitted That Met QC Criteria: February 2, 2012
• First Posted (Estimate): February 3, 2012

Study Record Updates

• Last Update Posted (Estimate): May 7, 2012
• Last Update Submitted That Met QC Criteria: May 4, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Male Healthy Volunteers
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Anticoagulants; Lacosamide; Warfarin
• Other Study ID Numbers: EP0013; 2011-004911-21 (EudraCT Number)