A Trial to Evaluate the Efficacy and Safety of Adjunctive Therapy With Lacosamide in Adults With Partial-Onset Seizures

A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Lacosamide as Adjunctive Therapy in Japanese and Chinese Adults With Uncontrolled Partial-Onset Seizures With or Without Secondary Generalization

The purpose of this study is to evaluate the efficacy and safety of 200 and 400 mg/day of orally administered Lacosamide as adjunctive therapy compared with placebo in Japanese and Chinese adults with uncontrolled Partial-Onset Seizures with or without secondary generalization.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Partial Onset Seizures
• Intervention / Treatment: Drug: Placebo; Drug: Lacosamide 50 mg; Drug: Lacosamide 100 mg

• Study Type: Interventional
• Enrollment (Actual): 548
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • 86026
  • Beijing, China
    • 86027
  • Changchun, China
    • 86015
  • Chengdu, China
    • 86005
  • Chengdu, China
    • 86032
  • Chongqing, China
    • 86006
  • Dalian, China
    • 86031
  • Guanghzou, China
    • 86009
  • Guangzhou, China
    • 86007
  • Guangzhou, China
    • 86008
  • Guangzhou, China
    • 86013
  • Guangzhou, China
    • 86016
  • Hangzhou, China
    • 86014
  • Harbin, China
    • 86010
  • Jinan, China
    • 86019
  • Kunming, China
    • 86004
  • Nanchang, China
    • 86011
  • Nanchang, China
    • 86012
  • Nanjing, China
    • 86028
  • Qingdao, China
    • 86003
  • Shanghai, China
    • 86001
  • Shanghai, China
    • 86023
  • Shanghai, China
    • 86025
  • Shenyang, China
    • 86021
  • Shijiazhuang, China
    • 86020
  • Suzhou, China
    • 86022
  • Taiyuan, China
    • 86002
  • Wuhan, China
    • 86018
  • Wuhan, China
    • 86024
  • Xi'An, China
    • 86017
  • Xiamen, China
    • 86029
• Japan
  • Asaka, Japan
    • 81056
  • Fujisawa, Japan
    • 81030
  • Fukuoka, Japan
    • 81013
  • Fukuoka, Japan
    • 81054
  • Hachinohe, Japan
    • 81057
  • Hakodate, Japan
    • 81008
  • Hamamatsu, Japan
    • 81027
  • Himeji, Japan
    • 81004
  • Hiroshima, Japan
    • 81018
  • Iwanuma, Japan
    • 81019
  • Kagoshima, Japan
    • 81012
  • Kitakyusyu, Japan
    • 81033
  • Kobe, Japan
    • 81017
  • Kodaira, Japan
    • 81024
  • Kokubunji, Japan
    • 81010
  • Koushi, Japan
    • 81032
  • Kurume, Japan
    • 81014
  • Kyoto, Japan
    • 81047
  • Nagakute, Japan
    • 81035
  • Nagoya, Japan
    • 81028
  • Nagoya, Japan
    • 81029
  • Nara, Japan
    • 81040
  • Neyagawa, Japan
    • 81007
  • Niigata, Japan
    • 81002
  • Ohmura, Japan
    • 81046
  • Okayama, Japan
    • 81005
  • Osakasayama, Japan
    • 81009
  • Saitama, Japan
    • 81011
  • Sakai, Japan
    • 81042
  • Sapporo, Japan
    • 81025
  • Sapporo, Japan
    • 81048
  • Sapporo, Japan
    • 81053
  • Sendai, Japan
    • 81020
  • Sendai, Japan
    • 81031
  • Shimotsuke, Japan
    • 81021
  • Shimotsuke, Japan
    • 81022
  • Shinjuku, Japan
    • 81026
  • Shizuoka, Japan
    • 81003
  • Suita, Japan
    • 81023
  • Suita, Japan
    • 81051
  • Suita, Japan
    • 81052
  • Takatsuki, Japan
    • 81016
  • Toyonaka, Japan
    • 81006
  • Ube, Japan
    • 81050
  • Yamagata, Japan
    • 81001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has had an Electroencephalogram (EEG) and a brain Computerized Tomography (CT) scan or Magnetic Resonance Imaging (MRI) exam consistent with a Diagnosis of Epilepsy with Partial-Onset Seizures according to the International Classification of Epileptic Seizures (1981)
• Subject must have been observed to have Partial-Onset Seizures for at least the previous 2 years despite prior therapy with at least 2 Anti-Epileptic Drugs (AEDs)(concurrently or sequentially) and must have been observed to have on average at least 4 Partial-Onset Seizures per 28 days with a seizure-free phase no longer than 21 days in the 8-Week Period prior to entry into the Baseline Period. In the case of Simple Partial Seizures, only those with motor signs will be counted towards meeting the inclusion criterion
• Subjects must be on a stable dose regimen of at least 1, but no more than 3 AEDs (concurrent stable Vagus Nerve Stimulation (VNS) is not counted as an AED). The VNS must have been in place for at least 6 months prior to study entry. The dosage of concomitant AED therapy and the settings of the VNS must be kept constant for a period of at least 4 weeks prior to entry into the Baseline Period
• Minimum Body Weight of 40 kg

Exclusion Criteria:

• Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt) or has a suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening
• Subject has a current or previous diagnosis of Pseudo-Seizures, Conversion Disorders, or other non-epileptical events that could be confused with Seizures
• Subject has Seizures that are uncountable due to Clustering (ie, an episode lasting less than 30 minutes in which several Seizures occur with such frequency that the initiation and completion of each individual Seizure cannot be distinguished) during the 8-Week Period prior to Visit 1
• Subject has a history of Primary Generalized Seizures
• Subject with a history of Status Epilepticus within the 12-Months Period prior to Visit 1
• Subject who underwent surgery for Epilepsy within the 2 Years Period prior to Visit 1
• Subjects with cardiac, renal, hepatic, endocrinological dysfunction or psychiatric illness that may impair reliable participation in the study or necessitate the use of medication not allowed by the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Matching placebo for 16 weeks.	Drug: Placebo; Matching oral Placebo tablets twice daily for 16 weeks.
EXPERIMENTAL: Lacosamide 200 mg/day; Lacosamide treatment of 200 mg/day (100 mg bid (twice daily)) for 16 weeks.	Drug: Lacosamide 50 mg; Active Substance: Lacosamide; Pharmaceutical Form: Film-coated tablet; Concentration: 50 mg; Route of Administration: Oral use; Other Names: Vimpat; Drug: Lacosamide 100 mg; Active Substance: Lacosamide; Pharmaceutical Form: Film-coated tablet; Concentration: 100 mg; Route of Administration: Oral use; Other Names: Vimpat
EXPERIMENTAL: Lacosamide 400 mg/day; Lacosamide treatment of 400 mg/day (200 mg bid (twice daily)) for 16 weeks.	Drug: Lacosamide 50 mg; Active Substance: Lacosamide; Pharmaceutical Form: Film-coated tablet; Concentration: 50 mg; Route of Administration: Oral use; Other Names: Vimpat; Drug: Lacosamide 100 mg; Active Substance: Lacosamide; Pharmaceutical Form: Film-coated tablet; Concentration: 100 mg; Route of Administration: Oral use; Other Names: Vimpat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Partial-Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period	Partial-onset seizure (POS) frequency per 28 days was calculated as: POS frequency = (Number of POS over the specified time interval) / (Number of days in the interval with available diary data) x 28. A negative value in Change in Partial-onset seizure frequency indicates a reduction of Partial-onset seizure frequency from Baseline to the Maintenance Period.	8-week Baseline Period (Visit 1 to 3) and 12-week Maintenance Period (Visit 5 to 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Individual Patients Who Experience a 50 % or Greater Reduction in Seizure Frequency From Baseline to the Maintenance Period (50 % Responder Rate)		8-week Baseline Period (Visit 1 to 3) to the 12-week Maintenance Period (Visit 5 to 8)
Percent Change in Partial-Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period	Calculates as 28-day seizure frequency during the Maintenance Period - 28-day seizure frequency during the Baseline Period, divided by the 28-day seizure frequency during the Baseline Period with this quantity multiplied by 100. A negative value in percent change from Baseline indicates a decrease in Partial-Onset Seizure frequency from Baseline to the Maintenance Period.	8-week Baseline Period (Visit 1 to 3) to the 12-week Maintenance Period (Visit 5 to 8)
Change in Partial-Onset Seizure Frequency Per 28 Days From Baseline to the Treatment Period (i.e., Titration + Maintenance Period)	Partial-onset seizure (POS) frequency per 28 days was calculated as: POS frequency = (Number of POS over the specified time interval) / (Number of days in the interval with available diary data) x 28. A negative value in Change in Partial-onset seizure frequency indicates a reduction of Partial-onset seizure frequency from Baseline to the Treatment Period.	8-week Baseline Period (Visit 1 to 3) to the 16-week Treatment Period (Visit 3 to 8)

Collaborators and Investigators

• Sponsor: UCB Pharma SA
• Collaborators: UCB Japan Co. Ltd.

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.

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: October 17, 2012
• First Submitted That Met QC Criteria: October 17, 2012
• First Posted (ESTIMATE): October 19, 2012

Study Record Updates

• Last Update Posted (ACTUAL): August 25, 2017
• Last Update Submitted That Met QC Criteria: July 28, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Epilepsy; Partial Onset Seizures; Lacosamide
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lacosamide
• Other Study ID Numbers: EP0008; 2014-003622-41 (EUDRACT_NUMBER); JapicCTI-121988 (REGISTRY: JAPIC)