Trial Comparing the Efficacy and Safety of Lacosamide (LCM) to Carbamazepine Controlled-Release (CBZ-CR); Initial Monotherapy in Epilepsy; Subjects Aged 16 and Older (SP0993)

A Multicenter, Double-blind, Double-dummy, Randomized, Positive- Controlled Study Comparing the Efficacy and Safety of Lacosamide (200 to 600 mg/Day) to Controlled Release Carbamazepine (400 to 1200 mg/Day), Used as Monotherapy in Subjects (≥ 16 Years) Newly or Recently Diagnosed With Epilepsy and Experiencing Partial-onset or Generalized Tonic-clonic Seizures.

Compare efficacy and safety of Lacosamide (LCM) to Carbamazepine Controlled-Release (CBZ-CR) as monotherapy in newly or recently newly diagnosed subjects with a primary efficacy endpoint of 6-month seizure freedom. Noninferiority design to show a similar risk/benefit balance between Lacosamide (LCM) and Carbamazepine-CR (CBZ-CR).

Study Overview

• Status: Completed
• Conditions: Epilepsy; Monotherapy
• Intervention / Treatment: Drug: Lacosamide; Drug: Carbamazepine-Controlled Release

• Study Type: Interventional
• Enrollment (Actual): 888
• Phase: Phase 3

Expanded Access

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

Contacts and Locations

Study Locations

• Australia
  • Chatswood, Australia
    • 104
  • Clayton, Australia
    • 105
  • New South Wales
    • East Gosford, New South Wales, Australia
      • 106
    • Randwick, New South Wales, Australia
      • 109
    • Westmead, New South Wales, Australia
      • 102
  • Queensland
    • Herston, Queensland, Australia
      • 103
  • South Australia
    • Woodville, South Australia, Australia
      • 100
  • Victoria
    • Fitzroy, Victoria, Australia
      • 101
    • Heidelberg, Victoria, Australia
      • 108
• Belgium
  • Brugge, Belgium
    • 127
  • Brugge, Belgium
    • 134
  • Hasselt, Belgium
    • 128
  • Leuven, Belgium
    • 126
• Bulgaria
  • Blagoevgrad, Bulgaria
    • 805
  • Panagyurishte, Bulgaria
    • 807
  • Pleven, Bulgaria
    • 803
  • Russe, Bulgaria
    • 810
  • Sofia, Bulgaria
    • 806
  • Sofia, Bulgaria
    • 808
  • Sofia, Bulgaria
    • 811
  • Veliko Tarnovo, Bulgaria
    • 809
• Canada
  • Calgary, Canada
    • 155
  • Halifax Nova Scotia, Canada
    • 158
  • Hamilton, Canada
    • 156
  • Veilleux, Canada
    • 159
  • Newfoundland and Labrador
    • St John's, Newfoundland and Labrador, Canada
      • 153
  • Quebec
    • Greenfield Park, Quebec, Canada
      • 152
• Czechia
  • Brno, Czechia
    • 185
  • Ostrava - Vitkovice, Czechia
    • 190
  • Prague, Czechia
    • 189
  • Praha 5, Czechia
    • 184
  • Zlin, Czechia
    • 180
• Finland
  • Helsinki, Finland
    • 205
  • Kuopio, Finland
    • 207
• France
  • Nancy, France
    • 236
  • Paris, France
    • 233
  • Strasbourg, France
    • 231
  • Toulouse Cedex 9, France
    • 235
• Germany
  • Altenburg, Germany
    • 263
  • Aschaffenburg, Germany
    • 258
  • Bad Neustadt, Germany
    • 265
  • Berlin, Germany
    • 257
  • Berlin, Germany
    • 262
  • Berlin, Germany
    • 270
  • Göttingen, Germany
    • 260
  • Köln, Germany
    • 271
  • Leipzig, Germany
    • 269
  • Marburg, Germany
    • 256
  • Muenchen, Germany
    • 264
  • Münster, Germany
    • 261
  • Osnabruck, Germany
    • 259
• Greece
  • Alexandroupoli, Greece
    • 496
  • Ioannina, Greece
    • 495
  • Thessalonikis, Greece
    • 490
  • Thessaloníki, Greece
    • 493
• Hungary
  • Balassagyarmat, Hungary
    • 289
  • Budapest, Hungary
    • 283
  • Budapest, Hungary
    • 284
  • Debrecen, Hungary
    • 286
  • Gyor, Hungary
    • 282
  • Pecs, Hungary
    • 288
  • Szeged, Hungary
    • 285
  • Szekszárd, Hungary
    • 290
  • Szombathely, Hungary
    • 291
• Italy
  • Bari, Italy
    • 310
  • Modena, Italy
    • 309
  • Padova, Italy
    • 308
  • Prato, Italy
    • 314
  • Roma, Italy
    • 311
• Japan
  • Asaka-shi, Japan
    • 831
  • Hamamatsu-shi, Japan
    • 833
  • Kagoshima-shi, Japan
    • 834
  • Kamakura-shi, Japan
    • 844
  • Kawasaki-shi, Japan
    • 846
  • Kokubunji-shi, Japan
    • 829
  • Miyakonojo, Japan
    • 843
  • Nagoya-shi, Japan
    • 835
  • Nara-shi, Japan
    • 830
  • Okayama-shi, Japan
    • 837
  • Saitama-shi, Japan
    • 828
  • Sapporo, Japan
    • 847
  • Sapporo-shi, Japan
    • 836
  • Shizuoka-shi, Japan
    • 832
• Korea, Republic of
  • Busan, Korea, Republic of
    • 525
  • Daegu, Korea, Republic of
    • 521
  • Dajeon, Korea, Republic of
    • 518
  • Seoul, Korea, Republic of
    • 516
  • Seoul, Korea, Republic of
    • 517
  • Seoul, Korea, Republic of
    • 519
  • Seoul, Korea, Republic of
    • 520
  • Seoul, Korea, Republic of
    • 523
  • Seoul, Korea, Republic of
    • 524
• Latvia
  • Riga, Latvia
    • 751
• Lithuania
  • Alytus, Lithuania
    • 727
  • Kaunas, Lithuania
    • 724
  • Vilnius, Lithuania
    • 728
• Mexico
  • San Luis Potosí, Mexico
    • 547
• Philippines
  • Manila, Philippines
    • 673
  • Pasig City, Philippines
    • 672
  • Quezon City, Philippines
    • 676
• Poland
  • Gdańsk, Poland
    • 336
  • Katowice, Poland
    • 334
  • Katowice, Poland
    • 340
  • Lublin, Poland
    • 342
  • Poznan, Poland
    • 341
  • Szczecin, Poland
    • 338
  • Warsaw, Poland
    • 343
• Portugal
  • Coimbra, Portugal
    • 360
  • Lisboa, Portugal
    • 362
  • Lisboa, Portugal
    • 365
  • Porto, Portugal
    • 366
  • Santa Maria da Feira, Portugal
    • 361
• Romania
  • Bucuresti, Romania
    • 576
  • Cluj-Napoca, Romania
    • 569
  • Craiova, Romania
    • 578
  • Iasi, Romania
    • 570
  • Iasi, Romania
    • 579
  • Sibiu, Romania
    • 571
  • Sibiu, Romania
    • 577
  • Targu Mures, Romania
    • 572
• Russian Federation
  • Kazan, Russian Federation
    • 387
  • Kazan, Russian Federation
    • 389
  • Kirov, Russian Federation
    • 396
  • Moscow, Russian Federation
    • 394
  • Moscow, Russian Federation
    • 401
  • Nizhny Novgorod, Russian Federation
    • 390
  • Novosibirsk, Russian Federation
    • 392
  • Saint Petersburg, Russian Federation
    • 397
  • Saint-Petersburg, Russian Federation
    • 400
  • Smolensk, Russian Federation
    • 386
  • Yaroslavl, Russian Federation
    • 399
• Slovakia
  • Dolni Kubin, Slovakia
    • 594
  • Dubnica nad Vahom, Slovakia
    • 598
  • Hlohovec, Slovakia
    • 596
  • Krompachy, Slovakia
    • 600
  • Levoca, Slovakia
    • 595
  • Tornala, Slovakia
    • 599
  • Žilina, Slovakia
    • 601
• Spain
  • Badalona, Spain
    • 422
  • Barcelona, Spain
    • 413
  • La Laguna, Spain
    • 419
  • Madrid, Spain
    • 416
  • Madrid, Spain
    • 425
  • Madrid, Spain
    • 426
  • Murcia (El Palmar), Spain
    • 421
  • San Sebastian, Spain
    • 418
  • Santiago de Compostela, Spain
    • 414
  • Sevilla, Spain
    • 424
• Sweden
  • Göteborg, Sweden
    • 440
  • Stockholm, Sweden
    • 438
  • Umea, Sweden
    • 442
• Switzerland
  • Aarau, Switzerland
    • 651
  • Biel, Switzerland
    • 654
  • Lugano, Switzerland
    • 653
  • St. Gallen, Switzerland
    • 647
• Thailand
  • Bangkok, Thailand
    • 699
  • Bangkok, Thailand
    • 702
  • Bangkok, Thailand
    • 703
  • Khon Kaen, Thailand
    • 698
• Ukraine
  • Chernihiv, Ukraine
    • 622
  • Dnipropetrovsk, Ukraine
    • 628
  • Kharkov, Ukraine
    • 626
  • Luhansk, Ukraine
    • 621
  • Odesa, Ukraine
    • 625
  • Simferopol, Ukraine
    • 632
  • Vinnytsa, Ukraine
    • 633
• United Kingdom
  • Birmingham, United Kingdom
    • 466
  • Glasgow, United Kingdom
    • 472
  • Stoke-on-Trent, United Kingdom
    • 471
• United States
  • Alabama
    • Alabaster, Alabama, United States
      • 786
    • Huntsville, Alabama, United States
      • 799
  • Arizona
    • Phoenix, Arizona, United States
      • 780
  • Arkansas
    • Little Rock, Arkansas, United States
      • 777
  • Florida
    • Ocala, Florida, United States
      • 795
    • Panama City, Florida, United States
      • 789
    • Port Charlotte, Florida, United States
      • 776
  • Kansas
    • Manhattan, Kansas, United States
      • 779
  • North Carolina
    • Charlotte, North Carolina, United States
      • 874
    • Hickory, North Carolina, United States
      • 876
    • Raleigh, North Carolina, United States
      • 873
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • 794
  • Texas
    • Mansfield, Texas, United States
      • 881
  • Wisconsin
    • Madison, Wisconsin, United States
      • 790
  • Wyoming
    • Casper, Wyoming, United States
      • 798

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject able to comply with study requirements
• Subject is 16 years and older (female; male). Minors will be included in countries only if legally permitted
• Subject has newly or recently diagnosed Epilepsy experiencing partial onset seizures (POS) or generalized tonic-clonic seizures with at least 2 unprovoked seizures separated by 48 hours in the 12 months preceding Visit 1 out of which at least 1 seizure occured 3 months preceding Visit 1
• Subject has had an Electroencephalogram (EEG) and a brain Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI) exam of the brain within the past 12 months. If the EEG and brain CT scan or MRI exam were not performed prior to Visit 1, they need to be completed and results must be available prior to randomization at Visit 2

Exclusion Criteria:

• Subject has a history or presence of seizures of other types than partial-onset (IA, IB, IC with clear focal origin) and generalized tonic-clonic (without clear focal origin) seizures (eg, myoclonic, absence)
• Subject has a history or presence of seizures occurring only in clustered patterns, defined as repeated seizures occurring over a short period of time (ie, < 20 minutes) with or without function regained between 2 ictal events
• Subject has a history, clinical, or Electroencephalogram (EEG) finding suggestive of Idiopathic Generalized Epilepsy (IGE) at randomization
• Subject has current or previous diagnosis of pseudoseizures, conversion disorders, or other nonepileptic ictal events that could be confused with seizures based on expert opinion and/or EEG evidence
• Subject has any medical or psychiatric condition
• Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has 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 received treatment with Phenobarbital or Primidone within 28 days prior to Visit 1
• Subject is taking Benzodiazepines for a nonepilepsy indication
• Subject has been treated for Epilepsy with any Antiepileptic Drug (AED) (including Benzodiazepines) in the last 6 months before Visit. However, acute and subacute seizure treatment is accepted with a maximum of 2 weeks duration and if treatment was stopped at least 3 days prior to randomization
• Prior use of Felbamate or Vigabatrin is not allowed
• Benzodiazepines as rescue therapy for Epilepsy may have been used as needed in this time period, but not more frequently than once per week
• Subject has a medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism, or excretion, has a history of alcohol or drug abuse within the previous 2 years
• Asian ancestry and tests positive for HLA-B*1502 allele
• Asian ancestry and tests positive for HLA-A*3101 allele

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lacosamide	Drug: Lacosamide; Lacosamide: Strengths: 50 mg / 100 mg; Form: tablets; Dosage: total daily target dose of 200 mg, 400 mg or 600 mg. 1 dose reduction was allowed from either 600 mg to 500 mg or from 400 mg to 300 mg total daily dose; Duration: up to 118 weeks; Other Names: Vimpat®
Active Comparator: Carbamazepine-Controlled Release (CBZ-CR)	Drug: Carbamazepine-Controlled Release; Carbamazepine-CR: Strengths: 200 mg; Form: tablets; Dosage: total daily target dose of 400 mg, 800 mg or 1200 mg. 1 dose reduction was allowed from either 1200 mg to 1000 mg or from 800 mg to 600 mg total daily dose; Duration: up to 118 weeks; Other Names: Tegretol® Retard Tablets 200 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects in the Full Analysis Set (FAS) Remaining Seizure Free for 6 Consecutive Months (26 Consecutive Weeks) of Treatment Following Stabilization at the Last Evaluated Dose for Each Subject	The proportion of subjects remaining seizure free for 6 months (26 weeks) was estimated using Kaplan-Meier methods.	6 consecutive months (26 consecutive weeks) of treatment following stabilization at the last evaluated dose for each subject
Proportion of Subjects in the Per Protocol Set (PPS) Remaining Seizure Free for 6 Consecutive Months (26 Consecutive Weeks) of Treatment Following Stabilization at the Last Evaluated Dose for Each Subject	The proportion of subjects remaining seizure free for 6 months (26 weeks) was estimated using Kaplan-Meier methods.	6 consecutive months (26 consecutive weeks) of treatment
Number of Subjects With at Least One Treatment-emergent Adverse Event (AE) During the Treatment Phase (up to 113 Weeks)	An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent AEs were defined as AEs that started on or after the date of first dose of study medication and within 30 days following the date of final study medication administration, or AEs whose intensity worsened on or after the date of first dose of study medication and within 30 days following the date of last dose.	Duration of the Treatment Phase (up to 113 weeks)
Number of Subjects Who Withdraw From the Study Due to a Treatment-emergent Adverse Event (AE) During the Treatment Phase (up to 113 Weeks)	An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent AEs were defined as AEs that started on or after the date of first dose of study medication and within 30 days following the date of final study medication administration, or AEs whose intensity worsened on or after the date of first dose of study medication and within 30 days following the date of last dose.	Duration of the Treatment Phase (up to 113 weeks)
Number of Subjects With at Least One Treatment-emergent Serious Adverse Event (SAE) During the Treatment Phase (up to 113 Weeks)	An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A Serious Adverse Event must meet 1 or more predefined criteria like death, life-threatening, etc. Treatment-emergent AEs were defined as AEs that started on or after the date of first dose of study medication and within 30 days following the date of final study medication administration, or AEs whose intensity worsened on or after the date of first dose of study medication and within 30 days following the date of last dose.	Duration of the Treatment Phase (up to 113 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Remaining Seizure Free for 12 Consecutive Months (52 Consecutive Weeks) Following Stabilization at the Last Evaluated Dose for Each Subject	The proportion of subjects remaining seizure free for 12 months (52 weeks) was estimated using Kaplan-Meier methods.	12 consecutive months of treatment following stabilization at the last evaluated dose for each subject

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES GmbH
• Collaborators: Eden Sarl

Publications and helpful links

General Publications

• Baulac M, Rosenow F, Toledo M, Terada K, Li T, De Backer M, Werhahn KJ, Brock M. Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol. 2017 Jan;16(1):43-54. doi: 10.1016/S1474-4422(16)30292-7. Epub 2016 Nov 24. Erratum In: Lancet Neurol. 2017 Feb;16(2):102.
• Mintzer S, Dimova S, Zhang Y, Steiniger-Brach B, De Backer M, Chellun D, Roebling R. Effects of lacosamide and carbamazepine on lipids in a randomized trial. Epilepsia. 2020 Dec;61(12):2696-2704. doi: 10.1111/epi.16745. Epub 2020 Nov 17.
• Lindauer A, Laveille C, Stockis A. Time-to-Seizure Modeling of Lacosamide Used in Monotherapy in Patients with Newly Diagnosed Epilepsy. Clin Pharmacokinet. 2017 Nov;56(11):1403-1413. doi: 10.1007/s40262-017-0530-8.

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: November 16, 2010
• First Submitted That Met QC Criteria: November 16, 2010
• First Posted (Estimate): November 18, 2010

Study Record Updates

• Last Update Posted (Actual): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Epilepsy; Monotherapy; Lacosamide; Vimpat®; Velocity
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Lacosamide; Carbamazepine
• Other Study ID Numbers: SP0993; 2010-019765-28 (EudraCT Number)