Clinical trial NCT01243177: Trial Comparing the Efficacy and Safety of Lacosamide (LCM) to Carbamazepine Controlled-Release (CBZ-CR); Initial Monotherapy in Epilepsy; Subjects Aged 16 and Older
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Monotherapy
Keywords: Lacosamide
Vimpat®
Epilepsy
Monotherapy
Velocity
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
Collaborators: name: Eden Sarl
First posted: 2010-11-18
Enrollment: 888
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 6 consecutive months (26 consecutive weeks) of treatment following stabilization at the last evaluated dose for each subject
measure: 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
timeFrame: 6 consecutive months (26 consecutive weeks) of treatment
measure: Number of Subjects With at Least One Treatment-emergent Adverse Event (AE) During the Treatment Phase (up to 113 Weeks)
timeFrame: Duration of the Treatment Phase (up to 113 weeks)
measure: Number of Subjects Who Withdraw From the Study Due to a Treatment-emergent Adverse Event (AE) During the Treatment Phase (up to 113 Weeks)
timeFrame: Duration of the Treatment Phase (up to 113 weeks)
measure: Number of Subjects With at Least One Treatment-emergent Serious Adverse Event (SAE) During the Treatment Phase (up to 113 Weeks)
timeFrame: Duration of the Treatment Phase (up to 113 weeks)
Secondary outcomes:
measure: Proportion of Subjects Remaining Seizure Free for 12 Consecutive Months (52 Consecutive Weeks) Following Stabilization at the Last Evaluated Dose for Each Subject
timeFrame: 12 consecutive months of treatment following stabilization at the last evaluated dose for each subject
Other outcomes:
Locations:
city: Alabaster
country: United States
facility: 786
state: Alabama
city: Huntsville
country: United States
facility: 799
state: Alabama
city: Phoenix
country: United States
facility: 780
state: Arizona
city: Little Rock
country: United States
facility: 777
state: Arkansas
city: Ocala
country: United States
facility: 795
state: Florida
city: Panama City
country: United States
facility: 789
state: Florida
city: Port Charlotte
country: United States
facility: 776
state: Florida
city: Manhattan
country: United States
facility: 779
state: Kansas
city: Charlotte
country: United States
facility: 874
state: North Carolina
city: Hickory
country: United States
facility: 876
state: North Carolina
city: Raleigh
country: United States
facility: 873
state: North Carolina
city: Oklahoma City
country: United States
facility: 794
state: Oklahoma
city: Mansfield
country: United States
facility: 881
state: Texas
city: Madison
country: United States
facility: 790
state: Wisconsin
city: Casper
country: United States
facility: 798
state: Wyoming
city: East Gosford
country: Australia
facility: 106
state: New South Wales
city: Randwick
country: Australia
facility: 109
state: New South Wales
city: Westmead
country: Australia
facility: 102
state: New South Wales
city: Herston
country: Australia
facility: 103
state: Queensland
city: Woodville
country: Australia
facility: 100
state: South Australia
city: Fitzroy
country: Australia
facility: 101
state: Victoria
city: Heidelberg
country: Australia
facility: 108
state: Victoria
city: Chatswood
country: Australia
facility: 104
city: Clayton
country: Australia
facility: 105
city: Brugge
country: Belgium
facility: 127
city: Brugge
country: Belgium
facility: 134
city: Hasselt
country: Belgium
facility: 128
city: Leuven
country: Belgium
facility: 126
city: Blagoevgrad
country: Bulgaria
facility: 805
city: Panagyurishte
country: Bulgaria
facility: 807
city: Pleven
country: Bulgaria
facility: 803
city: Russe
country: Bulgaria
facility: 810
city: Sofia
country: Bulgaria
facility: 806
city: Sofia
country: Bulgaria
facility: 808
city: Sofia
country: Bulgaria
facility: 811
city: Veliko Tarnovo
country: Bulgaria
facility: 809
city: St John's
country: Canada
facility: 153
state: Newfoundland and Labrador
city: Greenfield Park
country: Canada
facility: 152
state: Quebec
city: Calgary
country: Canada
facility: 155
city: Halifax Nova Scotia
country: Canada
facility: 158
city: Hamilton
country: Canada
facility: 156
city: Veilleux
country: Canada
facility: 159
city: Brno
country: Czechia
facility: 185
city: Ostrava - Vitkovice
country: Czechia
facility: 190
city: Prague
country: Czechia
facility: 189
city: Praha 5
country: Czechia
facility: 184
city: Zlin
country: Czechia
facility: 180
city: Helsinki
country: Finland
facility: 205
city: Kuopio
country: Finland
facility: 207
city: Nancy
country: France
facility: 236
city: Paris
country: France
facility: 233
city: Strasbourg
country: France
facility: 231
city: Toulouse Cedex 9
country: France
facility: 235
city: Altenburg
country: Germany
facility: 263
city: Aschaffenburg
country: Germany
facility: 258
city: Bad Neustadt
country: Germany
facility: 265
city: Berlin
country: Germany
facility: 257
city: Berlin
country: Germany
facility: 262
city: Berlin
country: Germany
facility: 270
city: Göttingen
country: Germany
facility: 260
city: Köln
country: Germany
facility: 271
city: Leipzig
country: Germany
facility: 269
city: Marburg
country: Germany
facility: 256
city: Muenchen
country: Germany
facility: 264
city: Münster
country: Germany
facility: 261
city: Osnabruck
country: Germany
facility: 259
city: Alexandroupoli
country: Greece
facility: 496
city: Ioannina
country: Greece
facility: 495
city: Thessalonikis
country: Greece
facility: 490
city: Thessaloníki
country: Greece
facility: 493
city: Balassagyarmat
country: Hungary
facility: 289
city: Budapest
country: Hungary
facility: 283
city: Budapest
country: Hungary
facility: 284
city: Debrecen
country: Hungary
facility: 286
city: Gyor
country: Hungary
facility: 282
city: Pecs
country: Hungary
facility: 288
city: Szeged
country: Hungary
facility: 285
city: Szekszárd
country: Hungary
facility: 290
city: Szombathely
country: Hungary
facility: 291
city: Bari
country: Italy
facility: 310
city: Modena
country: Italy
facility: 309
city: Padova
country: Italy
facility: 308
city: Prato
country: Italy
facility: 314
city: Roma
country: Italy
facility: 311
city: Asaka-shi
country: Japan
facility: 831
city: Hamamatsu-shi
country: Japan
facility: 833
city: Kagoshima-shi
country: Japan
facility: 834
city: Kamakura-shi
country: Japan
facility: 844
city: Kawasaki-shi
country: Japan
facility: 846
city: Kokubunji-shi
country: Japan
facility: 829
city: Miyakonojo
country: Japan
facility: 843
city: Nagoya-shi
country: Japan
facility: 835
city: Nara-shi
country: Japan
facility: 830
city: Okayama-shi
country: Japan
facility: 837
city: Saitama-shi
country: Japan
facility: 828
city: Sapporo-shi
country: Japan
facility: 836
city: Sapporo
country: Japan
facility: 847
city: Shizuoka-shi
country: Japan
facility: 832
city: Busan
country: Korea, Republic of
facility: 525
city: Daegu
country: Korea, Republic of
facility: 521
city: Dajeon
country: Korea, Republic of
facility: 518
city: Seoul
country: Korea, Republic of
facility: 516
city: Seoul
country: Korea, Republic of
facility: 517
city: Seoul
country: Korea, Republic of
facility: 519
city: Seoul
country: Korea, Republic of
facility: 520
city: Seoul
country: Korea, Republic of
facility: 523
city: Seoul
country: Korea, Republic of
facility: 524
city: Riga
country: Latvia
facility: 751
city: Alytus
country: Lithuania
facility: 727
city: Kaunas
country: Lithuania
facility: 724
city: Vilnius
country: Lithuania
facility: 728
city: San Luis Potosí
country: Mexico
facility: 547
city: Manila
country: Philippines
facility: 673
city: Pasig City
country: Philippines
facility: 672
city: Quezon City
country: Philippines
facility: 676
city: Gdańsk
country: Poland
facility: 336
city: Katowice
country: Poland
facility: 334
city: Katowice
country: Poland
facility: 340
city: Lublin
country: Poland
facility: 342
city: Poznan
country: Poland
facility: 341
city: Szczecin
country: Poland
facility: 338
city: Warsaw
country: Poland
facility: 343
city: Coimbra
country: Portugal
facility: 360
city: Lisboa
country: Portugal
facility: 362
city: Lisboa
country: Portugal
facility: 365
city: Porto
country: Portugal
facility: 366
city: Santa Maria da Feira
country: Portugal
facility: 361
city: Bucuresti
country: Romania
facility: 576
city: Cluj-Napoca
country: Romania
facility: 569
city: Craiova
country: Romania
facility: 578
city: Iasi
country: Romania
facility: 570
city: Iasi
country: Romania
facility: 579
city: Sibiu
country: Romania
facility: 571
city: Sibiu
country: Romania
facility: 577
city: Targu Mures
country: Romania
facility: 572
city: Kazan
country: Russian Federation
facility: 387
city: Kazan
country: Russian Federation
facility: 389
city: Kirov
country: Russian Federation
facility: 396
city: Moscow
country: Russian Federation
facility: 394
city: Moscow
country: Russian Federation
facility: 401
city: Nizhny Novgorod
country: Russian Federation
facility: 390
city: Novosibirsk
country: Russian Federation
facility: 392
city: Saint Petersburg
country: Russian Federation
facility: 397
city: Saint-Petersburg
country: Russian Federation
facility: 400
city: Smolensk
country: Russian Federation
facility: 386
city: Yaroslavl
country: Russian Federation
facility: 399
city: Dolni Kubin
country: Slovakia
facility: 594
city: Dubnica nad Vahom
country: Slovakia
facility: 598
city: Hlohovec
country: Slovakia
facility: 596
city: Krompachy
country: Slovakia
facility: 600
city: Levoca
country: Slovakia
facility: 595
city: Tornala
country: Slovakia
facility: 599
city: Žilina
country: Slovakia
facility: 601
city: Badalona
country: Spain
facility: 422
city: Barcelona
country: Spain
facility: 413
city: La Laguna
country: Spain
facility: 419
city: Madrid
country: Spain
facility: 416
city: Madrid
country: Spain
facility: 425
city: Madrid
country: Spain
facility: 426
city: Murcia (El Palmar)
country: Spain
facility: 421
city: San Sebastian
country: Spain
facility: 418
city: Santiago de Compostela
country: Spain
facility: 414
city: Sevilla
country: Spain
facility: 424
city: Göteborg
country: Sweden
facility: 440
city: Stockholm
country: Sweden
facility: 438
city: Umea
country: Sweden
facility: 442
city: Aarau
country: Switzerland
facility: 651
city: Biel
country: Switzerland
facility: 654
city: Lugano
country: Switzerland
facility: 653
city: St. Gallen
country: Switzerland
facility: 647
city: Bangkok
country: Thailand
facility: 699
city: Bangkok
country: Thailand
facility: 702
city: Bangkok
country: Thailand
facility: 703
city: Khon Kaen
country: Thailand
facility: 698
city: Chernihiv
country: Ukraine
facility: 622
city: Dnipropetrovsk
country: Ukraine
facility: 628
city: Kharkov
country: Ukraine
facility: 626
city: Luhansk
country: Ukraine
facility: 621
city: Odesa
country: Ukraine
facility: 625
city: Simferopol
country: Ukraine
facility: 632
city: Vinnytsa
country: Ukraine
facility: 633
city: Birmingham
country: United Kingdom
facility: 466
city: Glasgow
country: United Kingdom
facility: 472
city: Stoke-on-Trent
country: United Kingdom
facility: 471
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.