Bioavailability/Bioequivalence Study Between Lacosamide Tablet and Solution for Infusion in Healthy Japanese Subjects

A Single Center Open-label, Randomized, Single-dose, 3-way Crossover Study to Compare the Safety, Tolerability, and Pharmacokinetics of Lacosamide Administered as Oral Tablet or Intravenous Infusion in Healthy Japanese Subjects

This study will be conducted to compare the pharmacokinetics of Lacosamide (LCM) following a single 30-minute or 60-minute iv infusion of LCM 200 mg with those following a single oral dose of LCM 200 mg in healthy Japanese subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Lacosamide infusion; Drug: Lacosamide oral

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Middlesex
    • Harrow, Middlesex, United Kingdom
      • 001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Japanese male and female volunteers with the age between 20 and 55 years old

Exclusion Criteria:

• Subject has participated or is participating in any other clinical studies of investigational drug or another investigational medical product within the last 3 months
• Subject has a history (within 6 months) before screening visit of chronic alcohol and/or drug abuse and/or has smoked and/or has a history or presence of cardiovascular, respiratory, hepatic, renal, GI, endocrinological, or neurological disorders
• Subject has a history of suicide attempt or current active suicidal ideation
• Subject has experienced a myocardial infarction and/or made a blood donation or any other blood loss more than 400 ml in the last 3 months
• Subject is pregnant or nursing
• Subject is not healthy (eg, taking any drug treatments, having any medical or emotional/psychological problems, a drug/alcohol abuse, having abnormal safety parameters and/or was positive for HIV, HBsAg, HCV)
• Subject has an excessive use of alcohol or/and cigarettes and/or caffeine and/or abnormal diet and/or has taken grapefruit or grapefruit drink within 7 days before intake of Investigational Medicinal Product (IMP)
• Subject has a clinically significant abnormality in the 12-lead Electrocardiogram (ECG)
• Subject is having clinically relevant drug hypersensitivity to any components of the investigational medicinal product

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lacosamide 30-minute iv; A 30-minute intravenous constant infusion of Lacosamide (LCM) 200 mg (200 mg/20 mL single-use vial).	Drug: Lacosamide infusion; Strength: 10 mg/mL for infusion Form: solution for infusion Dosage: 200 mg, single dose Duration: 30-minute infusion or 60-minute infusion; Other Names: Vimpat
Experimental: Lacosamide 60-minute iv; 60-minute intravenous constant infusion of Lacosamide (LCM) 200 mg (200 mg/20 mL single-use vial).	Drug: Lacosamide infusion; Strength: 10 mg/mL for infusion Form: solution for infusion Dosage: 200 mg, single dose Duration: 30-minute infusion or 60-minute infusion; Other Names: Vimpat
Experimental: Lacosamide oral tablet; Oral administration of Lacosamide (LCM) 200 mg (2 x 100 mg film-coated tablet) with 200 mL of water.	Drug: Lacosamide oral; Strength: 200 mg Form: film-coated tablet Dosage: 200 mg, single dose Duration: single oral intake; Other Names: Vimpat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration of Lacosamide (Cmax) after oral and intravenous administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)
Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration of Lacosamide (AUC 0-t) after oral and intravenous administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration-time curve from zero up to infinity (AUC) after oral and intravenous administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)
Time to reach a maximum plasma concentration (tmax) after oral and intravenous administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)
Mean residence time (MRT) after oral and intravenous administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)
Rate constant of elimination (λz) after oral and intravenous administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)
Terminal half-life (t1/2) after oral and intravenous administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)
Apparent total body clearance (CL/F) after oral administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)
Total body clearance (CL) after intravenous administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)
Apparent volume of distribution (Vz/F) after oral administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)
Volume of distribution (Vz) after intravenous administration of Lacosamide	Pharmacokinetic samples will be taken at predose/preinfusion, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose (start of infusion)

Collaborators and Investigators

• Sponsor: UCB Pharma SA

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: November 11, 2013
• First Submitted That Met QC Criteria: November 11, 2013
• First Posted (Estimate): November 18, 2013

Study Record Updates

• Last Update Posted (Estimate): September 12, 2014
• Last Update Submitted That Met QC Criteria: September 11, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Bioequivalence; Japanese; Bioavailability; Lacosamide; Vimpat
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lacosamide
• Other Study ID Numbers: EP0036; 2012-003084-21 (EudraCT Number)