Clinical trial NCT06443463: Long-term Safety and Tolerability of BHV-7000
Official title: A Phase 2, Global, Multicenter, Long-term Safety Study Designed to Assess the Safety and Tolerability of BHV-7000 in Subjects With Refractory Focal Onset Epilepsy
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Focal Epilepsy
Keywords: Focal Epilepsy
Epilepsy
Seizure
Refractory Epilepsy
Partial Epilepsy
Lead sponsor: Biohaven Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2024-06-05
Enrollment: 660
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to determine if BHV- 7000 is safe and tolerable in adults with refractory focal onset epilepsy


Eligibility criteria: Key Inclusion Criteria:

* Subjects who completed the double-blind phase (DBP) of prior parent study, BHV7000-302 or BHV7000-303.
* (FOCBP) Females of Child Bearing Potential must have a negative urine pregnancy test at the Baseline/Day 0 visit

Key Exclusion Criteria:

* Any condition, such as an ongoing AE with/without sequelae, or is poorly tolerating IP in the double-blind phase of the parent study, that would interfere with the subject's ability to comply with study instructions, place the subject at unacceptable risk, and/or confound the interpretation of safety or efficacy data from the study, as judged by the Investigator.
* Any medical condition, based on the judgement of the Investigator, that would confound the ability to adequately assess safety and efficacy outcome measures

Primary outcomes:
measure: Number of Participants With Deaths, Serious AEs (SAEs), AEs Leading to Study Drug Discontinuation, and moderate or severe AEs
timeFrame: Up to 52 weeks
measure: Number of Subjects with Clinically Significant Laboratory Abnormalities
timeFrame: Up to 52 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Accel Research
state: Alabama
city: Phoenix
country: United States
facility: Xenoscience, Inc.
state: Arizona
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Phoenix
country: United States
facility: ARENSIA Exploratory Medicine
state: Arizona
city: Tucson
country: United States
facility: Center for Neurosciences
state: Arizona
city: Little Rock
country: United States
facility: Clinical Trials, Inc.
state: Arkansas
city: Rogers
country: United States
facility: WRN
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Lancaster
country: United States
facility: Amicis Research Center
state: California
city: Long Beach
country: United States
facility: Memorialcare Miller Children's & Women's Hospital Long Beach
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Pasadena
country: United States
facility: Profound Research LLC
state: California
city: Poway
country: United States
facility: Profound Research LLC
state: California
city: Aurora
country: United States
facility: Kaiser Permanente
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Anschultz Medical Campus
state: Colorado
city: Farmington
country: United States
facility: UConn Health
state: Connecticut
city: New Haven
country: United States
facility: Yale School of Medicine - Yale-New Haven Hospital
state: Connecticut
city: Boca Raton
country: United States
facility: EZR Research LLC
state: Florida
city: Bradenton
country: United States
facility: Nova Clinical Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: University of Florida (Jacksonville)
state: Florida
city: Kissimmee
country: United States
facility: Dm Healthworks
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Y&L Advance Health Care, Inc d/b/a Elite Clinical Research
state: Florida
city: Miami
country: United States
facility: Serenity Research Center
state: Florida
city: Miami
country: United States
facility: Floridian Research Institute
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Orlando
country: United States
facility: Research Institute of Orlando
state: Florida
city: Orlando
country: United States
facility: Comprehensive Neurology Clinic
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center
state: Florida
city: Rockledge
country: United States
facility: Knight Neurology
state: Florida
city: Tampa
country: United States
facility: PENS
state: Florida
city: Tampa
country: United States
facility: Santos Research Center
state: Florida
city: Weston
country: United States
facility: Encore Medical Research of Weston LLC.
state: Florida
city: Winter Park
country: United States
facility: Pediatrix Medical Group of Florida
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Boise
country: United States
facility: Consultants in Epilepsy & Neurology, PLLC
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Elgin
country: United States
facility: Revive Research Institute, Inc.
state: Illinois
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Lexington
country: United States
facility: Bluegrass Epilepsy Research
state: Kentucky
city: Baton Rouge
country: United States
facility: OLOLRMC
state: Louisiana
city: Baton Rouge
country: United States
facility: DelRicht Research
state: Louisiana
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Shreveport
country: United States
facility: LSU Health Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy & Sleep Center, LLC
state: Maryland
city: Silver Spring
country: United States
facility: Javara
state: Maryland
city: Boston
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: Rochester Hills
country: United States
facility: Revive Research Institute, Inc.
state: Michigan
city: Roseville
country: United States
facility: Minnesota Epilepsy Group, P.A.
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lincoln
country: United States
facility: Somnos Clinical Research
state: Nebraska
city: Hackensack
country: United States
facility: NEREG
state: New Jersey
city: Livingston
country: United States
facility: Inst of Neurology
state: New Jersey
city: Amherst
country: United States
facility: Dent Neurosciences Research Center
state: New York
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Hawthorne
country: United States
facility: BCHP
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: NYU
state: New York
city: New York
country: United States
facility: Northwell Health
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Medicine
state: New York
city: Woodmere
country: United States
facility: Five Towns Neuroscience Research
state: New York
city: Chapel Hill
country: United States
facility: UNC-Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: OnSite Clinical Solutions
state: North Carolina
city: Mooresville
country: United States
facility: Accellacare
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist
state: North Carolina
city: Canton
country: United States
facility: NeuroScience Research Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: OSU
state: Ohio
city: Springfield
country: United States
facility: Oregon Neurology Associates
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: AHN
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC
state: South Carolina
city: Chattanooga
country: United States
facility: WR-ClinSearch
state: Tennessee
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Cypress
country: United States
facility: Clinical Research Solutions LLC
state: Texas
city: Dallas
country: United States
facility: Neurology Consultants of Dallas, PA
state: Texas
city: El Paso
country: United States
facility: ANESC Research
state: Texas
city: Fort Worth
country: United States
facility: Tarrant Neurology Consultants
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center
state: Texas
city: Houston
country: United States
facility: UTHealth Houston
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: San Antonio
country: United States
facility: Road Runner Research, Ltd
state: Texas
city: Murray
country: United States
facility: Intermountain Health
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Burlington
country: United States
facility: UVM MC
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: McLean
country: United States
facility: Medstar Health Research Institute
state: Virginia
city: Richmond
country: United States
facility: Henrico Doctors Neurology Associates, LLC
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: STAT Research S.A.
state: Buenos Aires
city: Balvanera
country: Argentina
facility: Hospital General de Agudos Dr. José María Ramos Mejia
state: Ciudad Autónoma De BuenosAires
city: Buenos Aires
country: Argentina
facility: Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno CEMIC-Elías Galván 4102
state: Ciudad Autónoma De BuenosAires
city: Buenos Aires
country: Argentina
facility: Hospital Británico de Buenos Aires
state: Ciudad Autónoma De BuenosAires
city: San Miguel de Tucumán
country: Argentina
facility: Investigaciones Sanatorio Del Sur
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia - FLENI
city: Córdoba
country: Argentina
facility: Instituto Privado Kremer
city: Córdoba
country: Argentina
facility: Conci Carpinella - Santa Rosa N° 748
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne - PPDS
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Linz - Med Campus III
state: Oberösterreich
city: Salzburg
country: Austria
facility: Christian Doppler-Klinik - Universitätsklinikum der PMU
city: St. Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
city: Wien
country: Austria
facility: Medizinische Universitat Wien (Medical University of Vienna)
city: Edegem
country: Belgium
facility: UZ Antwerpen
state: Antwerpen
city: Anderlecht
country: Belgium
facility: Hôpital Erasme
state: Brussels
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
state: Brussels
city: Yvoir
country: Belgium
facility: CHU UCL Namur - Site Godinne
state: Namur
city: Gent
country: Belgium
facility: UZ Gent
state: Oost-Vlaanderen
city: Temuco
country: Chile
facility: Centro de especialidades médicas Vanguardia
state: Araucanía
city: Santiago
country: Chile
facility: Hospital Padre Hurtado
state: Región-MetropolitanadeSantiago
city: Santiago
country: Chile
facility: BIOCINETIC Ltda
state: Región-MetropolitanadeSantiago
city: Santiago
country: Chile
facility: Centro de Investigacion Clinica UC
state: Región-MetropolitanadeSantiago
city: Viña del Mar
country: Chile
facility: Instituto Neurologico Thalamus
state: Valparaíso
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Clinical Hospital Sveti duh
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Sestre Milosrdnice - Vinogradska cesta 29
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Zagreb
state: Grad Zagreb
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka - PPDS
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
state: Jihomoravský Kraj
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole
state: Praha, Hlavní Mesto
city: Odense
country: Denmark
facility: Odense Universitetshospital
state: Fyn
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala
state: Pirkanmaa
city: Kuopio
country: Finland
facility: Kuopion yliopistollinen sairaala
state: Pohjois-Savo
city: Helsinki
country: Finland
facility: Helsinki University Hospital
state: Uusimaa
city: Strasbourg
country: France
facility: CHU de Strasbourg - Hôpital de Hautepierre
state: Bas-Rhin
city: Dijon
country: France
facility: CHU Dijon Bourgogne
state: Côte-d'Or
city: Toulouse
country: France
facility: CHU de Toulouse-Hôpital Pierre-Paul Riquet-Site de Purpan
state: Haute-Garonne
city: Montpellier
country: France
facility: CHU de Montpellier- Hôpital Gui De Chauliac
state: Hérault
city: Tours
country: France
facility: CHRU de Tours - Hôpital Bretonneau
state: Indre-et-Loire
city: Nancy
country: France
facility: CHRU Nancy
state: Meurthe-et-Moselle
city: Lille Cedex
country: France
facility: CHU de Lille - Hopital Claude Huriez
state: Nord
city: Lyon
country: France
facility: Hospices Civils de Lyon - 59 Bd Pinel
state: Rhône
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
state: Baden-Württemberg
city: Kehl
country: Germany
facility: Epilepsiezentrum Kork
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: München
country: Germany
facility: LMU Klinikum der Universität München - Campus Großhadern
state: Bayern
city: Bernau bei Berlin
country: Germany
facility: Epilepsieklinik Tabor
state: Brandenburg
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann-Wolfgang Goethe-Universitat - Schleusenweg 2-16
state: Hessen
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH - Standort Marburg
state: Hessen
city: Osnabrück
country: Germany
facility: Klinikum Osnabrück GmbH
state: Niedersachsen
city: Bielefeld
country: Germany
facility: Krankenhaus Mara gGmbH
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Universitätsklinikum Münster
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
state: Sachsen
city: Radeberg
country: Germany
facility: Kleinwachau Sächsisches Epilepsiezentrum Radeberg Gemeinnützige Gmbh
state: Sachsen
city: Berlin
country: Germany
facility: Vivantes - Humboldt Klinikum
city: Ravensburg
country: Germany
facility: Epilepsie-Zentrum Bodensee
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Kozpont -Ret u.
state: Baranya
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont Kenezy Gyula Campus
state: Hajdú-Bihar
city: Budapest
country: Hungary
facility: Budapesti Bajcsy-Zsilinszky Korhaz es Rendelointezet
city: Budapest
country: Hungary
facility: SE INK Juhasz Pal Epilepszia Központ
city: Chieti
country: Italy
facility: Università degli Studi G. D'Annunzio Chieti-Pescara
state: Abruzzo
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Universitaria Renato Dulbecco - AO Mater Domini
state: Calabria
city: Napoli
country: Italy
facility: AORN Antonio Cardarelli
state: Campania
city: Bologna
country: Italy
facility: AUSL di Bologna - Ospedale Bellaria
state: Emilia-Romagna
city: Roma
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata
state: Lazio
city: Genova
country: Italy
facility: Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN
state: Liguria
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l. - PPDS
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
state: Lombardia
city: Milano
country: Italy
facility: ASST Santi Paolo e Carlo - Azienda Universitaria-Polo Universitario San Paolo
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Nazionale Casimiro Mondino IRCCS
state: Lombardia
city: Ancona
country: Italy
facility: Università Politecnica delle Marche Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
state: Marche
city: Baggiovara
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena - Ospedale Civile di Baggiovara
state: Modena
city: Pozzilli
country: Italy
facility: IRCCS Istituto Neurologico Mediterraneo Neuromed
state: Molise
city: Calambrone
country: Italy
facility: Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN
state: Toscana
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli-Rome
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesù - INCIPIT - PIN
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Di Verona
city: Heeze
country: Netherlands
facility: Kempenhaeghe - PPDS
state: Noord-Brabant
city: Heemstede
country: Netherlands
facility: Stichting Epilepsie Instellingen Nederland - Heemstede
state: Noord-Holland
city: Zwolle
country: Netherlands
facility: Stichting Epilepsie Instellingen Nederland - Dokter Denekampweg 20
state: Overijssel
city: Wrocław
country: Poland
facility: Przychodnia VISTAMED
state: Dolnoslaskie
city: Lublin
country: Poland
facility: Clinical Best Solutions - Lublin
state: Lubelskie
city: Świdnik
country: Poland
facility: NZOZ IGNIS dr med. Alicja Lobinska
state: Lubelskie
city: Nowa Sól
country: Poland
facility: Twoja Przychodnia Nowosolskie Centrum Medyczne sp. z o.o
state: Lubuskie
city: Łódź
country: Poland
facility: Santa Familia PTG Lodz
state: Lódzkie
city: Warszawa
country: Poland
facility: MTZ Clinical Research Powered by PRATIA - PPDS
state: Mazowieckie
city: Warszawa
country: Poland
facility: Neurosphera SP. Z O.O
state: Mazowieckie
city: Warszawa
country: Poland
facility: Instytut Psychiatrii i Neurologii
state: Mazowieckie
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI-House sp. z o.o.
state: Pomorskie
city: Poznań
country: Poland
facility: AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Poznaniu
state: Wielkopolskie
city: Gdańsk
country: Poland
facility: Copernicus Podmiot Leczniczy Sp. z o.o. - ul. Nowe Ogrody 1-6
city: Katowice
country: Poland
facility: Novo-Med Zielinski i wsp. Sp.J. - ul. Brynowska 44
city: Kraków
country: Poland
facility: Pratia MCM Kraków
city: Kraków
country: Poland
facility: LANDA Specjalistyczne Gabinety Lekarskie
city: Santa Maria Da Feira
country: Portugal
facility: ULS de Entre Douro e Vouga, EPE - Hospital de São Sebastião
state: Aveiro
city: Senhora da Hora
country: Portugal
facility: ULS de Matosinhos, EPE - Hospital Pedro Hispano
state: Porto
city: Braga
country: Portugal
facility: Centro Clínico Académico, Braga - Hospital de Braga
city: Coimbra
country: Portugal
facility: ULS de Coimbra, EPE - Hospitais da Universidade de Coimbra
city: Lisboa
country: Portugal
facility: ULS de Lisboa Ocidental, EPE - Hospital Egas Moniz
city: Lisboa
country: Portugal
facility: Hospital da Luz Torres de Lisboa
city: Maribor
country: Slovenia
facility: University Clinical Centre Maribor
city: Cape Town
country: South Africa
facility: InnoMed Clinical Trial Centre
state: Western Cape
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
state: Western Cape
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: Vigo
country: Spain
facility: CHUVI - H.U. Alvaro Cunqueiro
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Granada
country: Spain
facility: Hospital Universitario Clínico San Cecilio
city: Granada
country: Spain
facility: Hospital Vithas Granada
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: Madrid
country: Spain
facility: Hospital Ruber Internacional (Grupo Quironsalud)
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Hospital General
city: Sevilla
country: Spain
facility: Centro de Neurologia Avanzada
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
city: Zürich
country: Switzerland
facility: Klinik Lengg AG
state: Zürich (de)
city: Swansea
country: United Kingdom
facility: Morriston Hospital
state: Glamorgan
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital-PPDS
state: Glasgow City
city: Salford
country: United Kingdom
facility: Salford Royal Hospital - PPDS
state: Manchester
city: Liverpool
country: United Kingdom
facility: The Walton Centre - PPDS
state: Merseyside
city: London
country: United Kingdom
facility: University College Hospital
state: Middlesex
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
state: Oxfordshire
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: South Glamorgan
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
Study officials:
References: