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
- Conditions
- Epilepsy
- Interventions
- Other: Placebo TabletDrug: Lasosamide Oral SolutionOther: Placebo Oral Solution
- Registration Number
- NCT02408523
- Lead Sponsor
- UCB BIOSCIENCES, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 242
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lacosamide Lacosamide Tablet 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.) Lacosamide Lasosamide Oral Solution 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.) Placebo Placebo Oral Solution 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.) Placebo Placebo Tablet 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.)
- Primary Outcome Measures
Name Time Method 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) 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.
- Secondary Outcome Measures
Name Time Method Time to the First Primary Generalized Tonic Clonic (PGTC) Seizure During the Treatment Period From Visit 2 (Week 0) to Visit 10 (Week 24) 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.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) 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.
Percentage of Participants With at Least One Adverse Event (AE) as Reported Spontaneously by the Subject and/or Caregiver or Observed by the Investigator 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.
Plasma Concentrations of Lacosamide 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.
Trial Locations
- Locations (115)
Sp0982 018
🇺🇸Irvine, California, United States
Sp0982 034
🇺🇸Houston, Texas, United States
Sp0982 501
🇧🇬Sofia, Bulgaria
Sp0982 906
🇯🇵Fukuoka-shi, Japan
Sp0982 850
🇮🇱Reẖovot, Israel
Sp0982 903
🇯🇵Hamamatsu, Japan
Sp0982 902
🇯🇵Hiroshima, Japan
Sp0982 908
🇯🇵Shinjuku-Ku, Japan
Sp0982 655
🇵🇱Gdańsk, Poland
Sp0982 653
🇵🇱Katowice, Poland
Sp0982 658
🇵🇱Gdynia, Poland
Sp0982 656
🇵🇱Tyniec Mały, Poland
Sp0982 750
🇷🇺Kazan, Russian Federation
Sp0982 757
🇷🇺Ekaterinburg, Russian Federation
Sp0982 758
🇷🇺Pyatigorsk, Russian Federation
Sp0982 202
🇧🇪Gent, Belgium
Sp0982 200
🇧🇪Leuven, Belgium
Sp0982 005
🇺🇸Little Rock, Arkansas, United States
Sp0982 914
🇯🇵Kodaira, Japan
Sp0982 904
🇯🇵Shizuoka, Japan
Sp0982 911
🇯🇵Ōmura, Japan
Sp0982 015
🇺🇸Boise, Idaho, United States
Sp0982 023
🇺🇸Madison, Wisconsin, United States
Sp0982 981
🇦🇺Parkville, Victoria, Australia
Sp0982 907
🇯🇵Asaka, Japan
Sp0982 910
🇯🇵Gifu, Japan
Sp0982 912
🇯🇵Kagoshima, Japan
Sp0982 909
🇯🇵Kokubunji, Japan
Sp0982 900
🇯🇵Sapporo, Japan
Sp0982 657
🇵🇱Częstochowa, Poland
Sp0982 650
🇵🇱Warszawa, Poland
Sp0982 704
🇷🇴Iaşi, Romania
Sp0982 700
🇷🇴Timişoara, Romania
Sp0982 031
🇺🇸Colorado Springs, Colorado, United States
Sp0982 008
🇺🇸Santa Monica, California, United States
Sp0982 036
🇺🇸Danbury, Connecticut, United States
Sp0982 010
🇺🇸Waldorf, Maryland, United States
Sp0982 002
🇺🇸Port Charlotte, Florida, United States
Sp0982 985
🇦🇺Heidelberg, Australia
Sp0982 050
🇺🇸Greenville, Texas, United States
Sp0982 976
🇨🇳Changchun, China
Sp0982 975
🇨🇳Chongqing, China
Sp0982 185
🇧🇷Porto Alegre, Brazil
Sp0982 971
🇨🇳Beijing, China
Sp0982 973
🇨🇳Hangzhou, China
Sp0982 972
🇨🇳Shanghai, China
Sp0982 255
🇫🇷Bron, France
Sp0982 252
🇫🇷Lille Cedex, France
Sp0982 302
🇩🇪Muenchen, Germany
Sp0982 940
🇰🇷Daegu, Korea, Republic of
Sp0982 251
🇫🇷Nancy, France
Sp0982 305
🇩🇪Berlin, Germany
Sp0982 351
🇮🇹Torino, Italy
Sp0982 603
🇭🇺Szeged, Hungary
Sp0982 600
🇭🇺Budapest, Hungary
Sp0982 550
🇨🇿Ostrava poruba, Czechia
Sp0982 553
🇨🇿Praha, Czechia
Sp0982 556
🇨🇿Praha, Czechia
Sp0982 851
🇮🇱Tel HaShomer, Israel
Sp0982 913
🇯🇵Itami, Japan
Sp0982 901
🇯🇵Niigata, Japan
Sp0982 311
🇩🇪Marburg, Germany
Sp0982 707
🇷🇴Iaşi, Romania
Sp0982 402
🇪🇸Barcelona, Spain
Sp0982 960
🇨🇳Taipei, Taiwan
Sp0982 013
🇺🇸Panama City, Florida, United States
Sp0982 021
🇺🇸Peoria, Illinois, United States
Sp0982 042
🇺🇸Wellington, Florida, United States
Sp0982 944
🇰🇷Seoul, Korea, Republic of
Sp0982 045
🇺🇸Springfield, Illinois, United States
Sp0982 028
🇺🇸Alabaster, Alabama, United States
Sp0982 011
🇺🇸Jacksonville, Florida, United States
Sp0982 025
🇺🇸Golden Valley, Minnesota, United States
Sp0982 029
🇺🇸Saint Louis, Missouri, United States
Sp0982 043
🇺🇸New York, New York, United States
Sp0982 027
🇺🇸Renton, Washington, United States
Sp0982 980
🇦🇺Chatswood, Australia
Sp0982 986
🇦🇺Parkville, Australia
Sp0982 181
🇧🇷Curitiba, Brazil
Sp0982 186
🇧🇷Passo Fundo, Brazil
Sp0982 188
🇧🇷Rio De Janeiro, Brazil
Sp0982 180
🇧🇷Florianópolis, Brazil
Sp0982 183
🇧🇷São Paulo, Brazil
Sp0982 500
🇧🇬Blagoevgrad, Bulgaria
Sp0982 184
🇧🇷São Paulo, Brazil
Sp0982 097
🇨🇳Fuzhou, China
Sp0982 552
🇨🇿Zlín, Czechia
Sp0982 250
🇫🇷Rennes Cedex 9, France
Sp0982 303
🇩🇪Erlangen, Germany
Sp0982 314
🇩🇪Freiburg, Germany
Sp0982 406
🇪🇸Córdoba, Spain
Sp0982 941
🇰🇷Seoul, Korea, Republic of
Sp0982 161
🇲🇽Guadalajara, Mexico
Sp0982 451
🇵🇹Lisboa, Portugal
Sp0982 659
🇵🇱Warszawa, Poland
Sp0982 651
🇵🇱Katowice, Poland
Sp0982 755
🇷🇺Saint Petersburg, Russian Federation
Sp0982 756
🇷🇺Saint Petersburg, Russian Federation
Sp0982 753
🇷🇺Smolensk, Russian Federation
Sp0982 752
🇷🇺Samara, Russian Federation
Sp0982 821
🇸🇰Bardejov, Slovakia
Sp0982 823
🇸🇰Hlohovec, Slovakia
Sp0982 407
🇪🇸Madrid, Spain
Sp0982 403
🇪🇸Sevilla, Spain
Sp0982 961
🇨🇳Taichung, Taiwan
Sp0982 404
🇪🇸Málaga, Spain
Sp0982 201
🇧🇪Brussels, Belgium
Sp0982 652
🇵🇱Gliwice, Poland
Sp0982 654
🇵🇱Katowice, Poland
Sp0982 038
🇺🇸San Antonio, Texas, United States
Sp0982 035
🇺🇸Denver, Colorado, United States
Sp0982 009
🇺🇸New Orleans, Louisiana, United States
Sp0982 007
🇺🇸Bethesda, Maryland, United States
Sp0982 053
🇺🇸Austin, Texas, United States
Sp0982 047
🇺🇸San Antonio, Texas, United States