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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01526083
• Other study ID #: EP0013
• Secondary ID: 2011-004911-21
• Status: Completed
• Phase: Phase 1
• First received: January 31, 2012
• Last updated: May 4, 2012
• Start date: January 2012
• Est. completion date: March 2012

Study information

• Verified date: May 2012
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Other:
• Lacosamide
Strength: 200 mg, Form: Tablet, Frequency: Twice daily, Duration: 9 days
• 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

Locations

Country	Name	City	State
Netherlands	001	Zuidlaren

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	Maximum Warfarin plasma concentration (Cmax)		Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period	No
Primary	Maximum prothrombin time (PTmax)		Multiple sampling from 0 -168 hours following administration of a single warfarin dose in each treatment period	No
Primary	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	No
Primary	Warfarin maximum international normalized ratio (INRmax)		Multiple sampling from 0 -168 hours following administration of a single Warfarin dose in each treatment period	No
Primary	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	No
Secondary	Lacosamide trough plasma concentration (Ctrough)		Morning pre dose sample on Days 3-10 or Days 24 -30 of Lacosamide BID dosing	No
Secondary	Time of maximum Warfarin plasma concentration (Tmax)		Multiple sampling from 0 -168 hours following administration of a single Warfarin dose	No
Secondary	Terminal half-life of Warfarin (T ½)		Multiple sampling from 0 -168 hours following administration of a single Warfarin dose	No
Secondary	Apparent total body clearance of Warfarin (CL /F)		Multiple sampling from 0 -168 hours following administration of a single Warfarin dose	No
Secondary	Apparent volume of distribution of Warfarin (V /F)		Multiple sampling from 0 -168 hours following administration of a single Warfarin dose	No
Secondary	First order terminal elimination rate constant of Warfarin		Multiple sampling from 0 -168 hours following administration of a single Warfarin dose	No
Secondary	CYP2C9 genotype		Single measurement on Day 1	No
Secondary	VKORC1 genotype		Single measurement on Day 1	No
Secondary	Occurrence of at Least One Treatment-emergent Adverse Event (TEAE) during the duration of the study		Duration of study is approximately 32 days	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Change from Baseline in Pulse Rate at 12 h post dose	40-90 bpm	From pre dose to 12 h post dose LCM administration	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Change from Baseline in Systolic Blood Pressure at 4 h post dose		From pre dose to 4 h post dose LCM administration	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Change from Baseline in Diastolic Blood Pressure at 4 h post dose		From pre dose to 4 h post dose LCM administration	No
Secondary	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	No
Secondary	Change from Baseline in Body Temperature at 4h post dose		From pre dose to 4 h post dose Warfarin administration in each treatment period	No
Secondary	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	No
Secondary	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	No
Secondary	Change from Baseline in Body Temperature at 4 h post dose		From pre dose to 4 h post dose LCM administration	No
Secondary	Change from Baseline in Body Temperature at 12 h post dose	40-90 bpm	From pre dose to 12 h post dose LCM administration	No