Brivaracetam Efficacy and Safety Study in Subjects With Partial Onset Seizures

Epilepsy Clinical Trial

— BRITE  

Official title:

A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study to Evaluate the Efficacy and Safety of Brivaracetam in Subjects (≥16 to 80 Years Old) With Partial Onset Seizures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01261325
• Other study ID #: N01358
• Secondary ID: 2010-019361-28
• Status: Completed
• Phase: Phase 3
• Start date: December 2010
• Est. completion date: May 2014

Study information

• Verified date: July 2022
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of brivaracetam at doses of 100 and 200mg/day compared to placebo as adjunctive treatment in adult focal epilepsy subjects with partial onset seizures not fully controlled despite current treatment with 1 or 2 concomitant antiepileptic drugs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 768
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 80 Years

Eligibility

Inclusion Criteria:

• Well-characterized focal epilepsy/epileptic syndrome according to the 1989 International League Against Epilepsy (ILAE) classification

• Presence of an EEG reading compatible with the clinical diagnosis of focal epilepsy within the last 5 years

• Presence of a brain MRI/computed tomography (CT) scan performed within the last 2 years

• Subjects having at least 8 Type I seizures [POS; focal seizures (according to the 1981 ILAE classification)] during the 8-week Baseline Period with at least 2 Type I seizures during each 4-week interval of the Baseline Period

• Subjects having at least 2 partial onset seizures whether or not secondarily generalized per month during the 3 months preceding V1

• Subjects being uncontrolled while treated by 1 or 2 permitted concomitant AED(s). Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED

• Permitted concomitant AED(s) and VNS being stable and at optimal dosage for the subject from at least 1 month (3 months for phenobarbital, phenytoin, and primidone) before V1 and expected to be kept stable during the Baseline and Treatment Period. Benzodiazepine taken more than once a week (for any indication) will be considered as a concomitant AED

Exclusion Criteria:

• Subject previously randomized within this study or any other prior study with BRV as a dosing arm

• Seizure type IA (1981 ILAE classification) nonmotor as only seizure type.

• Subject is currently treated with LEV or has taken LEV within 90 days prior to V1

• Subject has any medical or psychiatric condition, obvious cognitive impairment or mental retardation that, in the opinion of the Investigator, could jeopardize or would compromise the subject's ability to participate in this study

• Subjects whose seizures could not be reliably counted on a regular basis due to their fast and repetitive occurrence (clusters or flurries)

• Subject has history or presence of status epilepticus during the year preceding V1 or during Baseline

• Subject has history or presence of known psychogenic nonepileptic seizures

• Subject on felbamate with less than 18 months exposure before V1

• Subject currently on vigabatrin. Subject with history of vigabatrin use but either no visual fields examination report available including standard static (Humphrey or Octopus) or kinetic perimetry (Goldman) or results of these examinations are abnormal

• Subject taking any drug with possible central nervous system (CNS) effects except if stable from at least 1 month before V1 and expected to be kept stable during the Treatment Period

• Subject has history of cerebrovascular accident, including transient ischemic attack, in the last 6 months

• Subject is suffering from severe cardiovascular disease or peripheral vascular disease

• Subject has a lifetime history of suicide attempt or has suicidal ideation in the past 6 months

• Subject has ongoing psychiatric disease other than mild controlled disorder

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

Drug:
• Placebo
Daily oral dose of two equal intakes of placebo in a double-blinded way for the 12-week treatment period
• Brivaracetam
Daily oral dose of two equal intakes of Brivaracetam 100 mg/ day in a double-blinded way for the 12-week treatment period
• Brivaracetam
Daily oral dose of two equal intakes of Brivaracetam 200 mg/ day in a double-blinded way for the 12-week treatment period.
• Antiepileptic drugs with market authorization available per country

Locations

Country	Name	City	State
Austria	202	Innsbruck
Austria	201	Linz
Austria	200	Wien
Austria	203	Wien
Belgium	226	Hechteleksel
Belgium	227	Leuven
Belgium	228	Liege
Brazil	104	Belo Horizonte
Brazil	100	Florianopolis
Brazil	103	Riberao Preto
Brazil	101	Sao Paulo
Bulgaria	294	Blagoevrad
Bulgaria	286	Sofiya
Bulgaria	287	Sofiya
Canada	075	Calgary	Alberta
Canada	077	Greenfield Park	Quebec
Canada	078	London	Ontario
Canada	079	Montreal	Quebec
Canada	080	Saskatoon	Saskatchewan
Canada	076	Toronto	Ontario
Czechia	916	Kromeriz
Czechia	251	Ostrava
Czechia	256	Ostrava
Czechia	913	Ostrava Poruba
Czechia	252	Praha 1
Czechia	253	Praha 4
Czechia	250	Zlin
Estonia	650	Tallinn
Estonia	652	Tallinn
Estonia	653	Tallinn
Estonia	651	Tartu
Finland	275	Kuopio
Finland	278	Oulu
Finland	276	Tampere
Finland	277	Turku
France	301	Bethune
France	308	Marseille
France	305	Montpellier
Germany	329	Berlin
Germany	326	Bernau
Germany	332	Bielefeld
Germany	902	Erlangen
Germany	331	Goettingen
Germany	904	Kehl-Kork
Germany	327	Kiel
Germany	900	Marburg
Germany	335	Muenchen
Germany	334	Osnabruck
Germany	330	Ravensburg
Germany	328	Ulm
Hong Kong	701	Hong Kong
Hong Kong	700	Shatin
Hungary	410	Budapest
Hungary	411	Budapest
Hungary	412	Budapest
Hungary	414	Debrecen
Hungary	413	Kecskemet
India	726	Bangalore
India	727	Hyderabad	Andhra Pradesh
India	729	Madurai
India	725	Mumbai	Maharastra
India	728	Mumbai	Maharastra
India	731	Nashik	Maharashtra
Italy	378	Bari
Italy	380	Firenze
Italy	379	Milano
Italy	377	Monserrato	Cagliari
Italy	386	Napoli
Italy	376	Perugia
Italy	375	Pisa
Italy	383	Pozzilli
Italy	384	Reggio Calabria
Italy	382	Torino
Japan	855	Hiroshima
Japan	852	Itami-city
Japan	850	Osaka
Japan	851	Shizuoka
Japan	854	Yokohama-City
Korea, Republic of	753	Busan
Korea, Republic of	752	Gwangju
Korea, Republic of	750	Seoul
Korea, Republic of	751	Seoul
Korea, Republic of	754	Seoul
Latvia	627	Daugapils
Latvia	629	Jekabpils
Latvia	626	Riga
Latvia	628	Riga
Latvia	625	Valmiera
Lithuania	425	Alytus
Lithuania	427	Kaunas
Lithuania	426	Vilnius
Mexico	129	Aguascalientes
Mexico	127	Culiacan
Mexico	125	Distrito Federal
Mexico	126	Guadalajara	Jalisco
Mexico	128	Guadalajara	Jalisco
Mexico	130	Mexico D.F.
Netherlands	401	Heemstede
Netherlands	400	Heeze
Netherlands	403	Zwolle
Poland	475	Bialystok
Poland	485	Gdansk
Poland	791	Gdansk
Poland	478	Katowice
Poland	480	Katowice
Poland	481	Katowice
Poland	476	Krakow
Poland	793	Krakow
Poland	483	Lublin
Poland	477	Poznan
Poland	479	Poznan
Poland	482	Poznan
Poland	488	Warszawa
Puerto Rico	038	San Juan
Russian Federation	501	Kazan
Russian Federation	506	Kazan
Russian Federation	502	Moscow
Russian Federation	503	Moscow
Russian Federation	505	Moscow
Russian Federation	509	Nizhny Novgorod
Russian Federation	508	Smolensk
Spain	536	Badalona
Spain	528	Barcelona
Spain	529	Barcelona
Spain	535	Barcelona
Spain	540	Barcelona
Spain	539	San Sebastian
Spain	532	Santiago de Compostela
Spain	527	Valencia
Spain	537	Valencia
Spain	526	Valladolid
Sweden	551	Goteborg
Sweden	552	Linkoping
Sweden	550	Stockholm
Taiwan	806	Kaohsiung City
Taiwan	801	Taichung
Taiwan	800	Tainan
Taiwan	803	Taoyuan Hsien
United Kingdom	603	Birmingham
United Kingdom	606	Cardiff
United Kingdom	601	Cornwall
United Kingdom	600	London
United Kingdom	605	Middlesborough
United Kingdom	607	Newcastle
United Kingdom	608	Salford
United Kingdom	602	Swansea
United States	020	Ames	Iowa
United States	050	Arlington	Texas
United States	010	Asheville	North Carolina
United States	023	Atlanta	Georgia
United States	063	Atlanta	Georgia
United States	060	Aurora	Colorado
United States	061	Austin	Texas
United States	008	Bethesda	Maryland
United States	039	Boise	Idaho
United States	096	Canton	Ohio
United States	089	Casper	Wyoming
United States	028	Charleston	South Carolina
United States	036	Charlottesville	Virginia
United States	034	Cleveland	Ohio
United States	085	Colorado Springs	Colorado
United States	062	Columbus	Georgia
United States	070	Columbus	Ohio
United States	011	Dallas	Texas
United States	035	Dallas	Texas
United States	003	Durham	North Carolina
United States	055	East Lansing	Michigan
United States	009	Golden Valley	Minnesota
United States	042	Hamilton	New Jersey
United States	092	Hammond	Louisiana
United States	049	Houston	Texas
United States	069	Iowa City	Iowa
United States	095	Kingston	New York
United States	032	Lebanon	New Hampshire
United States	780	Lexington	Kentucky
United States	775	Little Rock	Arkansas
United States	052	Madison	Wisconsin
United States	071	Miami	Florida
United States	110	Miami	Florida
United States	057	Milwaukee	Wisconsin
United States	051	Missoula	Montana
United States	073	Naples	Florida
United States	022	New York	New York
United States	099	New York	New York
United States	090	Ocala	Florida
United States	043	Oklahoma City	Oklahoma
United States	091	Oklahoma City	Oklahoma
United States	027	Orlando	Florida
United States	005	Peoria	Illinois
United States	015	Philadelphia	Pennsylvania
United States	001	Phoenix	Arizona
United States	013	Phoenix	Arizona
United States	064	Port Charlotte	Florida
United States	021	Port Royal	South Carolina
United States	098	Poughkeepsie	New York
United States	048	Rome	Georgia
United States	045	Sacramento	California
United States	025	San Francisco	California
United States	044	Sarasota	Florida
United States	033	Seattle	Washington
United States	056	Spokane	Washington
United States	002	Toledo	Ohio
United States	006	Tucson	Arizona
United States	054	Tulsa	Oklahoma
United States	058	Voorhees	New Jersey
United States	068	Waldorf	Maryland
United States	017	Winfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Czechia,  Estonia,  Finland,  France,  Germany,  Hong Kong,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  Netherlands,  Poland,  Puerto Rico,  Russian Federation,  Spain,  Sweden,  Taiwan,  United Kingdom, 

References & Publications (13)

Asadi-Pooya AA, Sperling MR, Chung S, Klein P, Diaz A, Elmoufti S, Schiemann J, Whitesides J. Efficacy and tolerability of adjunctive brivaracetam in patients with prior antiepileptic drug exposure: A post-hoc study. Epilepsy Res. 2017 Mar;131:70-75. doi: — View Citation

Ben-Menachem E, Mameniškiene R, Quarato PP, Klein P, Gamage J, Schiemann J, Johnson ME, Whitesides J, McDonough B, Eckhardt K. Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies. Neurology. 2016 Jul 19;87(3):314-23 — View Citation

Benbadis S, Klein P, Schiemann J, Diaz A, Elmoufti S, Whitesides J. Efficacy, safety, and tolerability of brivaracetam with concomitant lamotrigine or concomitant topiramate in pooled Phase III randomized, double-blind trials: A post-hoc analysis. Epileps — View Citation

Brandt C, Borghs S, Elmoufti S, Mueller K, Townsend R, de la Loge C. Health-related quality of life in double-blind Phase III studies of brivaracetam as adjunctive therapy of focal seizures: A pooled, post-hoc analysis. Epilepsy Behav. 2017 Apr;69:80-85. — View Citation

Brodie MJ, Fakhoury T, McDonough B, Colson AO, Stockis A, Elmoufti S, Whitesides J. Brivaracetam-induced elevation of carbamazepine epoxide levels: A post-hoc analysis from the clinical development program. Epilepsy Res. 2018 Sep;145:55-62. doi: 10.1016/j — View Citation

Brodie MJ, Whitesides J, Schiemann J, D'Souza J, Johnson ME. Tolerability, safety, and efficacy of adjunctive brivaracetam for focal seizures in older patients: A pooled analysis from three phase III studies. Epilepsy Res. 2016 Nov;127:114-118. doi: 10.10 — View Citation

Klein P, Johnson ME, Schiemann J, Whitesides J. Time to onset of sustained =50% responder status in patients with focal (partial-onset) seizures in three phase III studies of adjunctive brivaracetam treatment. Epilepsia. 2017 Feb;58(2):e21-e25. doi: 10.11 — View Citation

Klein P, Laloyaux C, Elmoufti S, Gasalla T, Martin MS. Time course of 75%-100% efficacy response of adjunctive brivaracetam. Acta Neurol Scand. 2020 Aug;142(2):175-180. doi: 10.1111/ane.13287. Epub 2020 Jun 9. — View Citation

Klein P, Schiemann J, Sperling MR, Whitesides J, Liang W, Stalvey T, Brandt C, Kwan P. A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with — View Citation

Moseley BD, Dimova S, Elmoufti S, Laloyaux C, Asadi-Pooya AA. Long-term efficacy and tolerability of adjunctive brivaracetam in adults with focal to bilateral tonic-clonic (secondary generalized) seizures: Post hoc pooled analysis. Epilepsy Res. 2021 Oct; — View Citation

Moseley BD, Sperling MR, Asadi-Pooya AA, Diaz A, Elmouft S, Schiemann J, Whitesides J. Efficacy, safety, and tolerability of adjunctive brivaracetam for secondarily generalized tonic-clonic seizures: Pooled results from three Phase III studies. Epilepsy R — View Citation

Ryvlin P, Dimova S, Elmoufti S, Floricel F, Laloyaux C, Nondonfaz X, Biton V. Tolerability and efficacy of adjunctive brivaracetam in adults with focal seizures by concomitant antiseizure medication use: Pooled results from three phase 3 trials. Epilepsia — View Citation

Toledo M, Whitesides J, Schiemann J, Johnson ME, Eckhardt K, McDonough B, Borghs S, Kwan P. Safety, tolerability, and seizure control during long-term treatment with adjunctive brivaracetam for partial-onset seizures. Epilepsia. 2016 Jul;57(7):1139-51. do — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Reduction Over Placebo for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration	Primary endpoint: United States of America (FDA)	12 week Treatment Period
Primary	50% Responder Rate for Partial Onset Seizure (Type I) Frequency Over the Treatment Period Standardized to a 28-day Duration	Primary Endpoint: European Regulatory Authorities A responder is a participant who experienced a 50% or greater reduction in partial onset seizure (Type I) frequency over the Treatment Period standardized to a 28-day duration.	Baseline to 12 week Treatment Period
Secondary	Percent Change in Partial Onset Seizure (Type I) Frequency From the Baseline to the Treatment Period		Baseline to 12 week Treatment Period
Secondary	Categorized Percent Reduction Form Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the Treatment Period		Baseline to 12 week Treatment Period
Secondary	Seizure Freedom Rate (All Seizure Types) During the 12-week Treatment Period		12 week Treatment Period
Secondary	All Seizure Frequency (Type I + II + III) During the 12-week Treatment Period		12 week Treatment Period
Secondary	Time to the First Type I Seizure During the Treatment Period		12 week Treatment Period
Secondary	Time to the Fifth Type I Seizure During the Treatment Period		12 week Treatment Period
Secondary	Time to the Tenth Type I Seizure During the Treatment Period		12 week Treatment Period

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