Trial Comparing the Efficacy and Safety of Lacosamide (LCM) to Carbamazepine Controlled-Release (CBZ-CR); Initial Monotherapy in Epilepsy; Subjects Aged 16 and Older
- Conditions
- EpilepsyMonotherapy
- Interventions
- Drug: Carbamazepine-Controlled Release
- Registration Number
- NCT01243177
- Lead Sponsor
- UCB BIOSCIENCES GmbH
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 888
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Carbamazepine-Controlled Release (CBZ-CR) Carbamazepine-Controlled Release - Lacosamide Lacosamide -
- Primary Outcome Measures
Name Time Method 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 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.
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 6 consecutive months (26 consecutive weeks) of treatment The proportion of subjects remaining seizure free for 6 months (26 weeks) was estimated using Kaplan-Meier methods.
Number of Subjects With at Least One Treatment-emergent Adverse Event (AE) During the Treatment Phase (up to 113 Weeks) Duration of 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.
Number of Subjects Who Withdraw From the Study Due to a Treatment-emergent Adverse Event (AE) During the Treatment Phase (up to 113 Weeks) Duration of 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.
Number of Subjects With at Least One Treatment-emergent Serious Adverse Event (SAE) During the Treatment Phase (up to 113 Weeks) Duration of 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.
- Secondary Outcome Measures
Name Time Method Proportion of Subjects Remaining Seizure Free for 12 Consecutive Months (52 Consecutive Weeks) Following Stabilization at the Last Evaluated Dose for Each Subject 12 consecutive months of treatment 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.
Trial Locations
- Locations (184)
881
🇺🇸Mansfield, Texas, United States
263
🇩🇪Altenburg, Germany
260
🇩🇪Göttingen, Germany
338
🇵🇱Szczecin, Poland
362
🇵🇹Lisboa, Portugal
576
🇷🇴Bucuresti, Romania
570
🇷🇴Iasi, Romania
180
🇨🇿Zlin, Czechia
780
🇺🇸Phoenix, Arizona, United States
786
🇺🇸Alabaster, Alabama, United States
794
🇺🇸Oklahoma City, Oklahoma, United States
134
🇧🇪Brugge, Belgium
128
🇧🇪Hasselt, Belgium
790
🇺🇸Madison, Wisconsin, United States
159
🇨🇦Veilleux, Canada
236
🇫🇷Nancy, France
231
🇫🇷Strasbourg, France
184
🇨🇿Praha 5, Czechia
127
🇧🇪Brugge, Belgium
126
🇧🇪Leuven, Belgium
155
🇨🇦Calgary, Canada
108
🇦🇺Heidelberg, Victoria, Australia
259
🇩🇪Osnabruck, Germany
829
🇯🇵Kokubunji-shi, Japan
525
🇰🇷Busan, Korea, Republic of
803
🇧🇬Pleven, Bulgaria
152
🇨🇦Greenfield Park, Quebec, Canada
265
🇩🇪Bad Neustadt, Germany
189
🇨🇿Prague, Czechia
310
🇮🇹Bari, Italy
185
🇨🇿Brno, Czechia
830
🇯🇵Nara-shi, Japan
235
🇫🇷Toulouse Cedex 9, France
832
🇯🇵Shizuoka-shi, Japan
106
🇦🇺East Gosford, New South Wales, Australia
846
🇯🇵Kawasaki-shi, Japan
156
🇨🇦Hamilton, Canada
495
🇬🇷Ioannina, Greece
490
🇬🇷Thessalonikis, Greece
103
🇦🇺Herston, Queensland, Australia
109
🇦🇺Randwick, New South Wales, Australia
314
🇮🇹Prato, Italy
158
🇨🇦Halifax Nova Scotia, Canada
257
🇩🇪Berlin, Germany
833
🇯🇵Hamamatsu-shi, Japan
104
🇦🇺Chatswood, Australia
262
🇩🇪Berlin, Germany
311
🇮🇹Roma, Italy
101
🇦🇺Fitzroy, Victoria, Australia
628
🇺🇦Dnipropetrovsk, Ukraine
285
🇭🇺Szeged, Hungary
496
🇬🇷Alexandroupoli, Greece
387
🇷🇺Kazan, Russian Federation
831
🇯🇵Asaka-shi, Japan
844
🇯🇵Kamakura-shi, Japan
835
🇯🇵Nagoya-shi, Japan
521
🇰🇷Daegu, Korea, Republic of
309
🇮🇹Modena, Italy
837
🇯🇵Okayama-shi, Japan
523
🇰🇷Seoul, Korea, Republic of
284
🇭🇺Budapest, Hungary
836
🇯🇵Sapporo-shi, Japan
727
🇱🇹Alytus, Lithuania
728
🇱🇹Vilnius, Lithuania
673
🇵🇭Manila, Philippines
336
🇵🇱Gdańsk, Poland
571
🇷🇴Sibiu, Romania
847
🇯🇵Sapporo, Japan
672
🇵🇭Pasig City, Philippines
334
🇵🇱Katowice, Poland
520
🇰🇷Seoul, Korea, Republic of
389
🇷🇺Kazan, Russian Federation
394
🇷🇺Moscow, Russian Federation
416
🇪🇸Madrid, Spain
798
🇺🇸Casper, Wyoming, United States
390
🇷🇺Nizhny Novgorod, Russian Federation
396
🇷🇺Kirov, Russian Federation
799
🇺🇸Huntsville, Alabama, United States
777
🇺🇸Little Rock, Arkansas, United States
795
🇺🇸Ocala, Florida, United States
789
🇺🇸Panama City, Florida, United States
779
🇺🇸Manhattan, Kansas, United States
776
🇺🇸Port Charlotte, Florida, United States
874
🇺🇸Charlotte, North Carolina, United States
876
🇺🇸Hickory, North Carolina, United States
873
🇺🇸Raleigh, North Carolina, United States
102
🇦🇺Westmead, New South Wales, Australia
100
🇦🇺Woodville, South Australia, Australia
105
🇦🇺Clayton, Australia
806
🇧🇬Sofia, Bulgaria
190
🇨🇿Ostrava - Vitkovice, Czechia
207
🇫🇮Kuopio, Finland
233
🇫🇷Paris, France
258
🇩🇪Aschaffenburg, Germany
270
🇩🇪Berlin, Germany
256
🇩🇪Marburg, Germany
269
🇩🇪Leipzig, Germany
271
🇩🇪Köln, Germany
261
🇩🇪Münster, Germany
264
🇩🇪Muenchen, Germany
289
🇭🇺Balassagyarmat, Hungary
493
🇬🇷Thessaloníki, Greece
308
🇮🇹Padova, Italy
834
🇯🇵Kagoshima-shi, Japan
843
🇯🇵Miyakonojo, Japan
828
🇯🇵Saitama-shi, Japan
518
🇰🇷Dajeon, Korea, Republic of
751
🇱🇻Riga, Latvia
516
🇰🇷Seoul, Korea, Republic of
517
🇰🇷Seoul, Korea, Republic of
519
🇰🇷Seoul, Korea, Republic of
547
🇲🇽San Luis Potosí, Mexico
360
🇵🇹Coimbra, Portugal
577
🇷🇴Sibiu, Romania
397
🇷🇺Saint Petersburg, Russian Federation
401
🇷🇺Moscow, Russian Federation
392
🇷🇺Novosibirsk, Russian Federation
598
🇸🇰Dubnica nad Vahom, Slovakia
596
🇸🇰Hlohovec, Slovakia
386
🇷🇺Smolensk, Russian Federation
400
🇷🇺Saint-Petersburg, Russian Federation
594
🇸🇰Dolni Kubin, Slovakia
399
🇷🇺Yaroslavl, Russian Federation
601
🇸🇰Žilina, Slovakia
425
🇪🇸Madrid, Spain
426
🇪🇸Madrid, Spain
422
🇪🇸Badalona, Spain
413
🇪🇸Barcelona, Spain
421
🇪🇸Murcia (El Palmar), Spain
418
🇪🇸San Sebastian, Spain
419
🇪🇸La Laguna, Spain
424
🇪🇸Sevilla, Spain
414
🇪🇸Santiago de Compostela, Spain
440
🇸🇪Göteborg, Sweden
438
🇸🇪Stockholm, Sweden
653
🇨🇭Lugano, Switzerland
442
🇸🇪Umea, Sweden
651
🇨🇭Aarau, Switzerland
702
🇹🇭Bangkok, Thailand
654
🇨🇭Biel, Switzerland
647
🇨🇭St. Gallen, Switzerland
703
🇹🇭Bangkok, Thailand
622
🇺🇦Chernihiv, Ukraine
625
🇺🇦Odesa, Ukraine
632
🇺🇦Simferopol, Ukraine
621
🇺🇦Luhansk, Ukraine
471
🇬🇧Stoke-on-Trent, United Kingdom
633
🇺🇦Vinnytsa, Ukraine
466
🇬🇧Birmingham, United Kingdom
472
🇬🇧Glasgow, United Kingdom
524
🇰🇷Seoul, Korea, Republic of
365
🇵🇹Lisboa, Portugal
805
🇧🇬Blagoevgrad, Bulgaria
290
🇭🇺Szekszárd, Hungary
807
🇧🇬Panagyurishte, Bulgaria
291
🇭🇺Szombathely, Hungary
724
🇱🇹Kaunas, Lithuania
676
🇵🇭Quezon City, Philippines
340
🇵🇱Katowice, Poland
341
🇵🇱Poznan, Poland
366
🇵🇹Porto, Portugal
286
🇭🇺Debrecen, Hungary
288
🇭🇺Pecs, Hungary
342
🇵🇱Lublin, Poland
343
🇵🇱Warsaw, Poland
569
🇷🇴Cluj-Napoca, Romania
599
🇸🇰Tornala, Slovakia
810
🇧🇬Russe, Bulgaria
808
🇧🇬Sofia, Bulgaria
811
🇧🇬Sofia, Bulgaria
809
🇧🇬Veliko Tarnovo, Bulgaria
282
🇭🇺Gyor, Hungary
361
🇵🇹Santa Maria da Feira, Portugal
572
🇷🇴Targu Mures, Romania
698
🇹🇭Khon Kaen, Thailand
283
🇭🇺Budapest, Hungary
205
🇫🇮Helsinki, Finland
578
🇷🇴Craiova, Romania
579
🇷🇴Iasi, Romania
600
🇸🇰Krompachy, Slovakia
595
🇸🇰Levoca, Slovakia
699
🇹🇭Bangkok, Thailand
626
🇺🇦Kharkov, Ukraine
153
🇨🇦St John's, Newfoundland and Labrador, Canada