Clinical trial NCT01526083: Effect of Lacosamide 200 mg Twice a Day (Bid) on Single Dose Warfarin 25 mg in Healthy Males
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Male Healthy Volunteers
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2012-02-03
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area under the Warfarin plasma concentration versus time curve from time 0 to infinity, AUC (Warfarin)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period
measure: Area under the Warfarin plasma concentration versus time curve from time 0 to the last quantifiable level, AUC0-t(Warfarin)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single warfarin dose in each treatment period
measure: Maximum Warfarin plasma concentration (Cmax)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period
measure: Maximum prothrombin time (PTmax)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single warfarin dose in each treatment period
measure: Warfarin area under the prothrombin time (PT) versus time curve (PTAUC)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single warfarin dose in each treatment period
measure: Warfarin maximum international normalized ratio (INRmax)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period
measure: Warfarin area under the International Normalized Ratio (INR) versus time curve (INRAUC)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period
Secondary outcomes:
measure: Lacosamide trough plasma concentration (Ctrough)
timeFrame: Morning pre dose sample on Days 3-10 or Days 24 -30 of Lacosamide BID dosing
measure: Time of maximum Warfarin plasma concentration (Tmax)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose
measure: Terminal half-life of Warfarin (T ½)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose
measure: Apparent total body clearance of Warfarin (CL /F)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose
measure: Apparent volume of distribution of Warfarin (V /F)
timeFrame: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose
measure: First order terminal elimination rate constant of Warfarin
timeFrame: Multiple sampling from 0 -168 hours following administration of a single Warfarin dose
measure: CYP2C9 genotype
timeFrame: Single measurement on Day 1
measure: VKORC1 genotype
timeFrame: Single measurement on Day 1
measure: Occurrence of at Least One Treatment-emergent Adverse Event (TEAE) during the duration of the study
timeFrame: Duration of study is approximately 32 days
measure: Change from Baseline in Pulse Rate at 4 h post dose
timeFrame: From pre dose to 4 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Pulse Rate at 12 h post dose
timeFrame: From pre dose to 12 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Pulse Rate at 24 h post dose
timeFrame: From pre dose to 24 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Pulse Rate at 4 h post dose
timeFrame: From pre dose to 4 h post dose Lacosamide (LCM) administration
measure: Change from Baseline in Pulse Rate at 12 h post dose
timeFrame: From pre dose to 12 h post dose LCM administration
measure: Change from Baseline in Systolic Blood Pressure at 4 h post dose
timeFrame: From pre dose to 4 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Systolic Blood Pressure at 12 h post dose
timeFrame: From pre dose to 12 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Systolic Blood Pressure at 24 h post dose
timeFrame: From pre dose to 24 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Systolic Blood Pressure at 4 h post dose
timeFrame: From pre dose to 4 h post dose LCM administration
measure: Change from Baseline in Systolic Blood Pressure at 12 h post dose
timeFrame: From pre dose to 12 h post dose LCM administration
measure: Change from Baseline in Diastolic Blood Pressure at 4 h post dose
timeFrame: From pre dose to 4 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Diastolic Blood Pressure at 12 h post dose
timeFrame: From pre dose to 12 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Diastolic Blood Pressure at 24 h post dose
timeFrame: From pre dose to 24 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Diastolic Blood Pressure at 4 h post dose
timeFrame: From pre dose to 4 h post dose LCM administration
measure: Change from Baseline in Diastolic Blood Pressure at 12 h post dose
timeFrame: From pre dose to 12 h post dose LCM administration
measure: Change from Baseline in Body Temperature at 4h post dose
timeFrame: From pre dose to 4 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Body Temperature at 12 h post dose
timeFrame: From pre dose to 12 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Body Temperature at 24 h post dose
timeFrame: From pre dose to 24 h post dose Warfarin administration in each treatment period
measure: Change from Baseline in Body Temperature at 4 h post dose
timeFrame: From pre dose to 4 h post dose LCM administration
measure: Change from Baseline in Body Temperature at 12 h post dose
timeFrame: From pre dose to 12 h post dose LCM administration
Other outcomes:
Locations:
city: Zuidlaren
country: Netherlands
facility: 001
Study officials:
affiliation: 1 877 822 9493
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References: