Efficacy and Safety of Rapid Titration Protocols of Lacosamide

Efficacy and Safety of Rapid Titration Protocols of Lacosamide: An Exploratory Study

Three different dose titration schedules are tested to find a way to reduce the titration period of lacosamide

Study Overview

• Status: Completed
• Conditions: Focal Epilepsy
• Intervention / Treatment: Drug: Lacosamide - conventional titration; Drug: Lacosamide - rapid titration 1; Drug: Lacosamide - rapid titration 2

Detailed Description

The investigators intend to find a way to reduce the titration period of lacosamide. Dosage of lacosamide is increased from 100-200 mg/d to 400 mg/d by three different titration schedule. Safety of lacosamide administration is primary endpoint. 50% responder rate (seizure reduction) and blood level of lacosamide are investigated for secondary endpoints.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 18-85 years old
• Patients diagnosed with focal epilepsy
• Patients subjected to the addition of lacosamide to treat focal onset seizures according to physician's judgement
• Subjects provided informed consent

Exclusion Criteria:

• Subjects who changed other antiepileptic drugs at the beginning of lacosamide treatment
• Subjects with unstable physical, mental or other disease condition that can impede with accurate evaluation or treatment
• Subjects with terminal illness or general medical condition that can impede with the participation of the clinical trial
• Subjects who do not agree with prior consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Conventional titration group	Drug: Lacosamide - conventional titration; Administration of lacosamide by the following schedule, Initial: 50 mg PO BID Increase dose at weekly intervals by 50 mg PO BID; up to 200 mg BID
EXPERIMENTAL: Rapid titration group 1	Drug: Lacosamide - rapid titration 1; Administration of lacosamide by the following schedule, Initial: 100 mg PO BID Increase dose to 200 mg BID after one week
EXPERIMENTAL: Rapid titration group 2	Drug: Lacosamide - rapid titration 2; Administration of lacosamide by the following schedule, Initial: 50 mg PO BID Increase dose every two days by 50 mg PO BID; up to 200 mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.	6 (rapid titration group) or 8 weeks (conventional titration group)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of seizure frequency	50% responder rate (percentage of patients achieving a 50% or greater reduction in seizure frequency)	Baseline, 6 weeks (rapid titration group) or 8 weeks (conventional titration group)
lacosamide drug level in the blood	lacosamide drug level 1 week after the day of the daily dose of lacosamide reaches 400 mg/day	2 weeks (rapid titration group) or 4 weeks (conventional titration group)

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Dongsan Medical Center; Konkuk University

Publications and helpful links

General Publications

• Doty P, Hebert D, Mathy FX, Byrnes W, Zackheim J, Simontacchi K. Development of lacosamide for the treatment of partial-onset seizures. Ann N Y Acad Sci. 2013 Jul;1291(1):56-68. doi: 10.1111/nyas.12213.
• Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007 Jul;48(7):1308-17. doi: 10.1111/j.1528-1167.2007.01188.x.
• Halasz P, Kalviainen R, Mazurkiewicz-Beldzinska M, Rosenow F, Doty P, Hebert D, Sullivan T; SP755 Study Group. Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial. Epilepsia. 2009 Mar;50(3):443-53. doi: 10.1111/j.1528-1167.2008.01951.x. Epub 2009 Jan 17.
• Chung S, Sperling MR, Biton V, Krauss G, Hebert D, Rudd GD, Doty P; SP754 Study Group. Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial. Epilepsia. 2010 Jun;51(6):958-67. doi: 10.1111/j.1528-1167.2009.02496.x. Epub 2010 Jan 27.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 3, 2018
• Primary Completion (ACTUAL): June 7, 2019
• Study Completion (ACTUAL): June 7, 2019

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (ACTUAL): July 31, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 18, 2020
• Last Update Submitted That Met QC Criteria: February 16, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lacosamide
• Other Study ID Numbers: 0620181410

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No