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

Epilepsy Clinical Trial

— SP0993  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01243177
• Other study ID #: SP0993
• Secondary ID: 2010-019765-28
• Status: Completed
• Phase: Phase 3
• Start date: April 2011
• Est. completion date: August 2015

Study information

• Verified date: January 2021
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 888
• Est. completion date: August 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Epilepsy
• Monotherapy

Intervention

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
• 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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
UCB BIOSCIENCES GmbH	Eden Sarl

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  Canada,  Czechia,  Finland,  France,  Germany,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  Spain,  Sweden,  Switzerland,  Thailand,  Ukraine,  United Kingdom, 

References & Publications (2)

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- — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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)
Primary	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)
Primary	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	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

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