A Study to Assess the Safety and Efficacy of Lacosamide Versus Placebo (a Pill Without Active Medication) in Patients With Idiopathic Generalised Epilepsy Who Are Already Taking Anti-epileptic Medications (VALOR)

November 26, 2020 updated by: UCB BIOSCIENCES, Inc.

A Double-blind, Randomized, Placebo-controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Lacosamide as Adjunctive Therapy for Uncontrolled Primary Generalized Tonic-Clonic Seizures in Subjects With Idiopathic Generalized Epilepsy

Evaluating efficacy & safety of lacosamide versus Placebo in a blinded fashion as add-on Therapy for Primary Generalized Tonic-clonic (PGTC) seizures in subject 4 years of age or greater with idiopathic generalized epilepsy currently taking 1 to 3 antiepileptic drugs. Maximum duration of study drug administration is 28 weeks. Eligible subjects may choose to enter the open-label extension study after completion.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

242

Phase

  • Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Chatswood, Australia
        • Sp0982 980
      • Heidelberg, Australia
        • Sp0982 985
      • Parkville, Australia
        • Sp0982 986
    • Victoria
      • Parkville, Victoria, Australia
        • Sp0982 981
  • Belgium
      • Brussels, Belgium
        • Sp0982 201
      • Gent, Belgium
        • Sp0982 202
      • Leuven, Belgium
        • Sp0982 200
  • Brazil
      • Curitiba, Brazil
        • Sp0982 181
      • Florianópolis, Brazil
        • Sp0982 180
      • Passo Fundo, Brazil
        • Sp0982 186
      • Porto Alegre, Brazil
        • Sp0982 185
      • Rio De Janeiro, Brazil
        • Sp0982 188
      • São Paulo, Brazil
        • Sp0982 183
      • São Paulo, Brazil
        • Sp0982 184
  • Bulgaria
      • Blagoevgrad, Bulgaria
        • Sp0982 500
      • Sofia, Bulgaria
        • Sp0982 501
  • China
      • Beijing, China
        • Sp0982 971
      • Changchun, China
        • Sp0982 976
      • Chongqing, China
        • Sp0982 975
      • Fuzhou, China
        • Sp0982 097
      • Hangzhou, China
        • Sp0982 973
      • Shanghai, China
        • Sp0982 972
  • Czechia
      • Ostrava poruba, Czechia
        • Sp0982 550
      • Praha, Czechia
        • Sp0982 553
      • Praha, Czechia
        • Sp0982 556
      • Zlín, Czechia
        • Sp0982 552
  • France
      • Bron, France
        • Sp0982 255
      • Lille Cedex, France
        • Sp0982 252
      • Nancy, France
        • Sp0982 251
      • Rennes Cedex 9, France
        • Sp0982 250
  • Germany
      • Berlin, Germany
        • Sp0982 305
      • Erlangen, Germany
        • Sp0982 303
      • Freiburg, Germany
        • Sp0982 314
      • Marburg, Germany
        • Sp0982 311
      • Muenchen, Germany
        • Sp0982 302
  • Hungary
      • Budapest, Hungary
        • Sp0982 600
      • Szeged, Hungary
        • Sp0982 603
  • Israel
      • Reẖovot, Israel
        • Sp0982 850
      • Tel HaShomer, Israel
        • Sp0982 851
  • Italy
      • Torino, Italy
        • Sp0982 351
  • Japan
      • Asaka, Japan
        • Sp0982 907
      • Fukuoka-shi, Japan
        • Sp0982 906
      • Gifu, Japan
        • Sp0982 910
      • Hamamatsu, Japan
        • Sp0982 903
      • Hiroshima, Japan
        • Sp0982 902
      • Itami, Japan
        • Sp0982 913
      • Kagoshima, Japan
        • Sp0982 912
      • Kodaira, Japan
        • Sp0982 914
      • Kokubunji, Japan
        • Sp0982 909
      • Niigata, Japan
        • Sp0982 901
      • Sapporo, Japan
        • Sp0982 900
      • Shinjuku-Ku, Japan
        • Sp0982 908
      • Shizuoka, Japan
        • Sp0982 904
      • Ōmura, Japan
        • Sp0982 911
  • Korea, Republic of
      • Daegu, Korea, Republic of
        • Sp0982 940
      • Seoul, Korea, Republic of
        • Sp0982 941
      • Seoul, Korea, Republic of
        • Sp0982 944
  • Mexico
      • Guadalajara, Mexico
        • Sp0982 161
  • Poland
      • Częstochowa, Poland
        • Sp0982 657
      • Gdańsk, Poland
        • Sp0982 655
      • Gdynia, Poland
        • Sp0982 658
      • Gliwice, Poland
        • Sp0982 652
      • Katowice, Poland
        • Sp0982 651
      • Katowice, Poland
        • Sp0982 653
      • Katowice, Poland
        • Sp0982 654
      • Tyniec Mały, Poland
        • Sp0982 656
      • Warszawa, Poland
        • Sp0982 650
      • Warszawa, Poland
        • Sp0982 659
  • Portugal
      • Lisboa, Portugal
        • Sp0982 451
  • Romania
      • Iaşi, Romania
        • Sp0982 704
      • Iaşi, Romania
        • Sp0982 707
      • Timişoara, Romania
        • Sp0982 700
  • Russian Federation
      • Ekaterinburg, Russian Federation
        • Sp0982 757
      • Kazan, Russian Federation
        • Sp0982 750
      • Pyatigorsk, Russian Federation
        • Sp0982 758
      • Saint Petersburg, Russian Federation
        • Sp0982 755
      • Saint Petersburg, Russian Federation
        • Sp0982 756
      • Samara, Russian Federation
        • Sp0982 752
      • Smolensk, Russian Federation
        • Sp0982 753
  • Slovakia
      • Bardejov, Slovakia
        • Sp0982 821
      • Hlohovec, Slovakia
        • Sp0982 823
  • Spain
      • Barcelona, Spain
        • Sp0982 402
      • Córdoba, Spain
        • Sp0982 406
      • Madrid, Spain
        • Sp0982 407
      • Málaga, Spain
        • Sp0982 404
      • Sevilla, Spain
        • Sp0982 403
  • Taiwan
      • Taichung, Taiwan
        • Sp0982 961
      • Taipei, Taiwan
        • Sp0982 960
  • United States
    • Alabama
      • Alabaster, Alabama, United States, 35007
        • Sp0982 028
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Sp0982 005
    • California
      • Irvine, California, United States, 92868
        • Sp0982 018
      • Santa Monica, California, United States, 90404
        • Sp0982 008
    • Colorado
      • Colorado Springs, Colorado, United States, 80910
        • Sp0982 031
      • Denver, Colorado, United States, 80202
        • Sp0982 035
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • Sp0982 036
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Sp0982 011
      • Panama City, Florida, United States, 32405
        • Sp0982 013
      • Port Charlotte, Florida, United States, 33952
        • Sp0982 002
      • Wellington, Florida, United States, 33470
        • Sp0982 042
    • Idaho
      • Boise, Idaho, United States, 83702
        • Sp0982 015
    • Illinois
      • Peoria, Illinois, United States, 61637
        • Sp0982 021
      • Springfield, Illinois, United States, 62702
        • Sp0982 045
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Sp0982 009
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Sp0982 007
      • Waldorf, Maryland, United States, 20603
        • Sp0982 010
    • Minnesota
      • Golden Valley, Minnesota, United States, 55422
        • Sp0982 025
    • Missouri
      • Saint Louis, Missouri, United States, 63131
        • Sp0982 029
    • New York
      • New York, New York, United States, 10016
        • Sp0982 043
    • Texas
      • Austin, Texas, United States, 78758
        • Sp0982 053
      • Greenville, Texas, United States, 75401
        • Sp0982 050
      • Houston, Texas, United States, 77025
        • Sp0982 034
      • San Antonio, Texas, United States, 78207
        • Sp0982 047
      • San Antonio, Texas, United States, 78229
        • Sp0982 038
    • Washington
      • Renton, Washington, United States, 98057
        • Sp0982 027
    • Wisconsin
      • Madison, Wisconsin, United States, 53715
        • Sp0982 023

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subject with a confirmed diagnosis at least 24 weeks prior to Visit 1 and a disease onset prior to 30 years of age, consistent with idiopathic generalized epilepsy (IGE) experiencing primary generalized tonic-clonic (PGTC) seizures (Type IIE) that are classifiable according to the International League Against Epilepsy (ILAE) Classification of Epileptic Seizures (ILAE, 1981)
  • Subject has >=3 PGTC seizures during the 16-week Combined Baseline (12-week Historical Baseline plus 4-week Prospective Baseline)
  • If a brain magnetic resonance imaging (MRI)/computed tomography (CT) scan has been performed, there must be no evidence of any progressive abnormality or any lesion likely to be associated with partial-onset seizures
  • Subject has been maintained on a stable dose regimen of 1 to 2 non-benzodiazepine marketed antiepileptic drugs (AEDs) with no benzodiazepine AEDs OR 1 benzodiazepine marketed AED with 1 to 2 non benzodiazepine marketed AEDs for at least 28 days prior to Visit 1 with or without additional concurrent stable vagus nerve stimulation (VNS)
  • Subjects are required to have had an electroencephalogram (EEG) report consistent with idiopathic generalized epilepsy (eg, generalized 3Hz epileptiform discharges and a normal EEG background) confirmed by a Central Reviewer

Exclusion Criteria:

  • Subject is receiving any investigational drugs or using any experimental devices in addition to Lacosamide (LCM)
  • Subject meets the withdrawal criteria for SP0982 or is experiencing an ongoing serious adverse event (SAE)
  • Subject has an active suicidal ideation as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the 'Since Last Visit' version of the Columbia-Suicide Severity Rating Scale (C-SSRS)
  • Subject has >=2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >ULN total bilirubin (>=1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin <35%)

For randomized subjects with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, a Baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic case report form (eCRF).

If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at screening, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of the subject must be discussed with the Medical Monitor.

Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated once for confirmation. This includes re-screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lacosamide

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day are allowed. Maximal dose 400 mg/day for adult subjects and pediatric subjects >= 50 kg.

Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric subjects < 30 kg.)

Lasosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric subjects 30 kg to < 50 kg.)
Drug: Lacosamide Tablet
  • Active Substance: Lacosamide
  • Pharmaceutical Form: Film-coated Tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use
Other Names:
  • Vimpat
Drug: Lasosamide Oral Solution
  • Active Substance: Lacosamide
  • Pharmaceutical Form: Oral Solution
  • Concentration: 10 mg/ml
  • Route of Administration: Oral use
Other Names:
  • Vimpat
Placebo Comparator: Placebo

Placebo 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day are allowed. Maximal dose 400mg/day for adult subjects and pediatric subjects >= 50kg.

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric subjects < 30kg.)

Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric subjects 30kg to < 50kg.)
Other: Placebo Tablet
  • Active Substance: Placebo
  • Pharmaceutical Form: Film-coated Tablet
  • Concentration: 50 mg
  • Route of Administration: Oral use
Other: Placebo Oral Solution
  • Active Substance: Placebo
  • Pharmaceutical Form: Oral Solution
  • Concentration: 10 mg/ml
  • Route of Administration: Oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to the Second Primary Generalized Tonic Clonic (PGTC) Seizure During the 24-week Treatment Period From Visit 2 (Week 0) to Visit 10 (Week 24)
Time Frame: During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)

The primary efficacy variable was the time to the second primary generalized tonic clonic seizure (PGTCS) during the 24-week Treatment Period. Relative difference between groups (Lacosamide vs Placebo) was expressed as Hazard Ratio.

The indicated measured values are the observed number of events of second PGTCS in the treatment period which form the basis of the statistical analysis of the time to event analysis.

The hazard ratio compares 2 treatment groups for the times to a specified number of events (125) for the combined treatment groups, and so both the number of events and the times until those events pertain to the computation of the hazard ratio.

A Hazard Ratio below 1 indicates time to second PGTCS was improved for LCM compared to Placebo.
During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Seizure Freedom for Primary Generalized Tonic Clonic (PGTC) Seizures During the 24-week Treatment Period From Visit 2 (Week 0) to Visit 10 (Week 24)
Time Frame: During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
A seizure-free day from primary generalized tonic clonic seizures (PGTCS) was defined as a day where no PGTCS were reported in the seizure diary and PGTCS were assessed, which was estimated using Kaplan-Meier (KM) methods.
During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
Time to the First Primary Generalized Tonic Clonic (PGTC) Seizure During the Treatment Period From Visit 2 (Week 0) to Visit 10 (Week 24)
Time Frame: During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)

The secondary efficacy variable was the time to the first primary generalized tonic clonic seizure (PGTCS) during the 24-week Treatment Period. Relative difference between groups (Lacosamide vs Placebo) was expressed as Hazard Ratio.

The indicated measured values are the observed number of events of first PGTCS in the treatment period which form the basis of the statistical analysis of the time to event analysis.

The hazard ratio compares 2 treatment groups for the times to the number of events for the combined treatment groups, and so both the number of events and the times until those events pertain to the computation of the hazard ratio.

A Hazard Ratio below 1 indicates time to second PGTCS was improved for LCM compared to Placebo.
During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
Percentage of Participants With at Least One Adverse Event (AE) as Reported Spontaneously by the Subject and/or Caregiver or Observed by the Investigator
Time Frame: From Visit 1 (Week -4) to End of Study Period (up to Week 36)
An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational medicinal product (IMP), whether or not related to the IMP.
From Visit 1 (Week -4) to End of Study Period (up to Week 36)
Plasma Concentrations of Lacosamide
Time Frame: During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)

Lacosamide plasma concentration was expressed in micrograms per milliliter (μg/mL).

Means and standard deviation (SD) were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint. Values Below Limit of Quantification (BLQ) were replaced by value of 0 in calculations of means and SDs.
During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UCB BIOSCIENCES, Inc.

Collaborators

Pharmaceutical Research Associates

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2015

Primary Completion (Actual)

April 1, 2019

Study Completion (Actual)

June 1, 2019

Study Registration Dates

First Submitted

March 31, 2015

First Submitted That Met QC Criteria

March 31, 2015

First Posted (Estimate)

April 3, 2015

Study Record Updates

Last Update Posted (Actual)

December 17, 2020

Last Update Submitted That Met QC Criteria

November 26, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SP0982
  • 2011-003100-21 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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