Comparison of Two Doses of Edoxaban Using Different Tests (Assays) and Clinical Outcomes

Atrial Fibrillation Clinical Trial

Official title:

Evaluation of Edoxaban in Anticoagulant Naïve Patients With Nonvalvular Atrial Fibrillation (NVAF) and High Creatinine Clearance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02964949
• Other study ID #: DU176b-C-E314
• Secondary ID: 2016-001795-30
• Status: Completed
• Phase: N/A
• Start date: January 24, 2017
• Est. completion date: October 9, 2018

Study information

• Verified date: December 2018
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Atrial fibrillation is when the heart's two upper chambers (called atria) beat chaotically and irregularly, out of coordination with the two lower chambers (called ventricles) of the heart. This can lead to blood clots forming in the heart chamber.

Patients with atrial fibrillation will be treated with either 60 mg or 75 mg of edoxaban for up to 12 months, with a 2-4 week follow-up, after which their participation is complete.

Blood samples will be collected before the first dose of study drug (Day 0), and on Days 30, 90 and 360 (at pre dose, 1-2 hours post dose and 4-8 hours post-dose).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 607
• Est. completion date: October 9, 2018
• Est. primary completion date: October 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Meets protocol-specified criteria for qualification

• Is able to follow the protocol specified contraception methods

• Is willing and able to comply with any restrictions related to food, drink and medications

• Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

Exclusion Criteria:

• Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters

• Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

1. the safety or well-being of the participant or study staff

2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding)

3. the analysis of results

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Edoxaban
Edoxaban will be provided in blister packs with active and placebo tablets maintaining the blind, i.e., one 60 mg active tablet and a 15 mg placebo or one 60 mg active tablet and a 15 mg active tablet. Transition doses of 30 mg + 15 mg edoxaban are provided in 14-tablet blister packs.

Locations

Country	Name	City	State
Belgium	O L V Ziekenhuis	Aalst
Belgium	ZNA Middelheim	Antwerpen
Belgium	AZ Sint-Jan Brugge	Brugge
Belgium	C H U Brugmann - Site Victor Horta	Bruxelles
Belgium	Jessa Ziekenhuis - Campus Virga Jesse	Hasselt
Belgium	St-Franciskus Ziekenhuis	Heusden-Zolder
Belgium	Universitairsitaire Ziekenhuizen Leuven	Leuven
Belgium	C H R de la Citadelle	Liege
Belgium	AZ Sint-Maarten	Mechelen
Belgium	AZ Turnhout - Campus Sint-Elisabeth	Turnhout
Bulgaria	MHAT 'Sveta Ekaterina' EOOD	Dimitrovgrad
Bulgaria	MHAT Dr Tota Venkova AD	Gabrovo
Bulgaria	Medical Center Haskovo EOOD	Haskovo
Bulgaria	MHAT-Haskovo AD	Haskovo
Bulgaria	MHAT - Pazardzhik AD	Pazardzhik
Bulgaria	MHAT Sv Pantaleymon - Pleven OOD	Pleven
Bulgaria	SHATC Pleven EAD	Pleven
Bulgaria	UMHAT 'Dr Georgi Stranski' EAD	Pleven
Bulgaria	MHAT-Plovdiv AD	Plovdiv
Bulgaria	UMHAT Sv Georgi EAD	Plovdiv
Bulgaria	Fifth MHAT - Sofia EAD	Sofia
Bulgaria	Fourth MHAT - Sofia EAD	Sofia
Bulgaria	MHAT - National Heart Hospital EAD	Sofia
Bulgaria	NMTH Tsar Boris III	Sofia
Bulgaria	Second MHAT - Sofia AD	Sofia
Bulgaria	UMHAT 'Sveta Anna' AD	Sofia
Bulgaria	UMHAT 'Tsaritsa Yoanna - ISUL' EAD	Sofia
Bulgaria	UMHAT Alexandrovska EAD	Sofia
Bulgaria	SHATC Cardiolife OOD	Varna
Croatia	General Hospital Dubrovnik	Dubrovnik
Croatia	General Hospital Dr Tomislav Bardek	Koprivnica
Croatia	Special Hospital for medical rehabilitation	Krapinske Toplice
Croatia	Clinical Hospital Centre Rijeka	Rijeka
Croatia	General Hospital Dr Josip Bencevic	Slavonski Brod
Croatia	General Hospital Varazdin	Varazdin
Croatia	General Hospital Zadar	Zadar
Croatia	Clinical Hospital Center Sestre Milosrdnice	Zagreb
Croatia	Clinical Hospital Dubrava	Zagreb
Croatia	Clinical Hospital Sveti Duh	Zagreb
Croatia	University Hospital center Zagreb (2108)	Zagreb
Croatia	University Hospital center Zagreb (2110)	Zagreb
Czechia	Innera s r o	Benesov
Czechia	Poliklinika Humanitas	Bilovec
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Edumed s.r.o	Broumov
Czechia	Nemocnice Havlickuv Brod, p.o.	Havlickuv Brod
Czechia	Kardio-Pisova, s.r.o.	Hradec Kralove
Czechia	Oblastni nemocnice Kolin, a.s.	Kolin
Czechia	Centrum pro choroby srdce a cev	Kromeriz
Czechia	Kromerizska nemocnice, a.s.	Kromeriz
Czechia	InterKardioML s r o	Marianske Lazne
Czechia	PV - kardiologie s.r.o.	Pardubice
Czechia	Corintez s.r.o	Prague
Czechia	Kardio-Pisova sro	Praha
Czechia	AVICENA -KARDIOLOGIE, INTERNA s.r.o.	Praha 1
Czechia	Nemocnice na Frantisku	Praha 1
Czechia	Ordince pro choroby srdce a cev	Praha 10
Czechia	Fakultni nemocnice v Motole	Praha 5
Czechia	Oblastni nemocnice Pribram, a.s.	Príbram
Czechia	Poliklinika RAVAK	Pribram 8
Czechia	Nemocnice Slany	Slany
Czechia	Poliklinika Masarykuv Dum, s.r.o.	Trutnov
Czechia	Clinical Trials Services s.r.o	Uherske Hradiste
Czechia	Krajska nemocnice T Bati a s	Zlin
Denmark	Bispebjeg og Fredeiksberg Hospital	Copenhagen
Denmark	Amager Hospital	Copenhagen S
Denmark	Gentofte Hospital	Hellerup
Denmark	Herlev Hospital	Herlev
Denmark	Holbæk Sygehus	Holbæk
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Rigshospitalet	København Ø
Denmark	Nykøbing F Sygehus	Nykøbing Falster
Denmark	Slagelse Sygehus	Slagelse
Denmark	Regionshospitalet Viborg	Viborg
Estonia	Dr Arvo Rosenthal LLC	Tallinn
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	North Estonia Medical Centre Foundation	Tallinn
Estonia	Tartu University Hospital	Tartu
Hungary	Principal SMO Kft	Baja
Hungary	Belgyogyaszati es Kardiologiai Maganrendelo	Bekescsaba
Hungary	Grof Tisza Istvan Korhaz	Berettyoujfalu
Hungary	Bajcsy-Zsilinszky Korhaz es Rendelointezet	Budapest
Hungary	Budai Irgalmasrendi Korhaz	Budapest
Hungary	Budapesti Szent Ferenc Korhaz	Budapest
Hungary	Nyiro Gyula Korhaz - Orszagos Pszichiatriai es Addiktologiai Intezet	Budapest
Hungary	Obudai Egeszsegugyi Centrum Kft	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Szent Margit Korhaz	Budapest
Hungary	Uzsoki Utcai Korhaz	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont (4002)	Debrecen
Hungary	Debreceni Egyetem Klinikai Kozpont (4025)	Debrecen
Hungary	Markhot Ferenc Oktatokorhaz es Rendelointezet	Eger
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyor
Hungary	Csongrad Megyei Egeszsegugyi Ellato Kozpont Hodmezovasarhely-Mako	Hodmezovasarhely
Hungary	Studium Egeszseghaz Kft	Kalocsa
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvar
Hungary	Bacs-Kiskun Megyei Korhaz	Kecskemet
Hungary	Selye Janos Korhaz	Komarom
Hungary	Kanizsai Dorottya Korhaz	Nagykanizsa
Hungary	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza
Hungary	Pecsi Tudomanyegyetem	Pecs
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Szekesfehervar
Hungary	Csongrad Megyei Dr Bugyi Istvan Korhaz	Szentes
Hungary	Jeruzsalemhegyi Egeszseghaz	Veszprem
Hungary	Zala Megyei Szent Rafael Korhaz	Zalaegerszeg
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	Dr Iveta Neniske GP Practice	Jekabpils
Latvia	Jelgava Outpatient Clinic	Jelgava
Latvia	Dr R Eglite`s Private practice	Kuldiga
Latvia	Inese Cebere GP practice	Liepaja
Latvia	Clinic of GP A Lasmanis ALMA	Riga
Latvia	GK Neiroklinika	Riga
Latvia	Health Centre 4	Riga
Latvia	Pauls Stradins Clinical University Hospital	Riga
Latvia	Dr D Harasimjuka GP Practice	Valmiera
Latvia	Regional Hospital of Ziemelkurzeme	Ventspils
Lithuania	Elite Medicale JSC	Kaunas
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics (5103)	Kaunas
Lithuania	Kaunas Clinical Hospital Public Institution	Kaunas
Lithuania	Saules Seimos Medicinos Centras JSC	Kaunas
Lithuania	Cardiology and Rehabilitation Clinic JSC	Klaipeda
Lithuania	Klaipeda Republican Hospital Public Institution	Klaipeda
Lithuania	Vilnius University Hospital Santariskiu Clinic Public Institution	Vilnius
Poland	CERMED	Bialystok
Poland	KLIMED Marek Klimkiewicz	Bialystok
Poland	KARDIOMED Janczska Kociwska Ostki PodckaRekrzSp	Elblag
Poland	Synexus Polska SCM Sp z o o Gdansku	Gdansk
Poland	Indywidualna Specjalistyczna Praktyka Lekarska w Dziedzinie Kardiologii lek med Krzysztof Cymerman	Gdynia
Poland	Synexus Polska Sp z o o Oddzial w Gdyni	Gdynia
Poland	Synexus Polska Sp z o o Oddzial w Katowicach	Katowice
Poland	Grazyna Pulka Specjalistyczny Osrodek ALL-MED	Krakow
Poland	Centrum Opieki Zdrowotnej Orkan-Med	Ksawerow
Poland	Gabinet Internistyczno-Kardiologiczny Dr n. med. Jacek Nowak	Libiaz
Poland	Polimedica Centrum Badan Profilaktyki I Leczenia	Lodz
Poland	Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lodz
Poland	KLIMED Marek Klimkiewicz	Lomza
Poland	Medicome Sp z o o	Oswiecim
Poland	SPZOZ w Pulawach Szpital Specjalistyczny	Pulawy
Poland	Janusz Spyra Specjalistyczna Praktyka Lekarska	Ruda Slaska
Poland	Centrum Medyczne Medyk	Rzeszow
Poland	Centrum Medyczne Sabamed - Rzeszów	Rzeszow
Poland	NZOZ Pro-Cordis Sopockie Centrum Bad Kardiolog	Sopot
Poland	Indywidualna Specjalistyczna Praktyka Lekarska B Busz-Papiez	Szczecin
Poland	Synexus Polska Sp z o o Oddzial w Warszawie	Warszawa
Poland	Synexus Polska Sp z o o Oddzial we Wroclawiu	Wroclaw
Poland	KO-MED Centra Kliniczne Zamosc	Zamosc
Russian Federation	TSHI Altay Territorial Cardiologocal dispensary	Barnaul
Russian Federation	City Hospital 1	Chelyabinsk
Russian Federation	Dep Clin Hosp on Station Kemerovo of OAO "Russian Railways	Kemerovo
Russian Federation	FSBI "Scientific-research Institute for Complex Problems of cardiovascular disease"	Kemerovo
Russian Federation	FSHI "MSU of MoIA of RF of Kemerovo Region"	Kemerovo
Russian Federation	FSBI Russian Cardiological Scientific and Industrial Complex of the MoH of the RF	Moscow
Russian Federation	SBIH of Moscow City Clinical Hospital 17	Moscow
Russian Federation	SBIH of Novosibirsk Region Clinical Emergency Hospital 2	Novosibirsk
Russian Federation	Ultramed	Omsk
Russian Federation	SBEI HPE Orenburg State Medical University of the MoH of the RF	Orenburg
Russian Federation	SPb SBIH City Hospital 38 n a N A Semashko	Pushkin
Russian Federation	SBI of Ryazan region Regional Clinical Cardiological Dispensary	Ryazan'
Russian Federation	FFSBI The Nikiforov Russian Center of Emergency and Radiation Medicine	Saint Petersburg
Russian Federation	FSBI Saint-Petersburg Multidisciplinary Centre	Saint Petersburg
Russian Federation	FSBIH SPb Clinical Hospital of RAS	Saint Petersburg
Russian Federation	LLC "Institute of Medical Investigations"	Saint Petersburg
Russian Federation	LLC Medical Institute on Krestovsky	Saint Petersburg
Russian Federation	North-West Federal Medical Research Center n a V A Almazov	Saint Petersburg
Russian Federation	Pavlov First Saint Petersburg State Medical University	Saint Petersburg
Russian Federation	SBI of HE Northwestern SMU n a I I Mechnikov	Saint Petersburg
Russian Federation	SHI "Center of Occupational Pathology"	Saint Petersburg
Russian Federation	SPb SBIH City Hospital 15	Saint Petersburg
Russian Federation	SPB SHI Pokrovskaya City Hospital	Saint Petersburg
Russian Federation	StP SHI Clinical hospital of St Luka	Saint Petersburg
Russian Federation	SBEI HPE Smolensk State Medical University of the MoH of the RF	Smolensk
Russian Federation	FSBI Research Institute for Cardiology of Siberian Branch RAMS	Tomsk
Russian Federation	SBIH of Yaroslavl region Regional Clinical Hospital	Yaroslavl'
Serbia	Clinical Center Bezanijska kosa	Belgrade
Serbia	Clinical Center Dr Dragisa Misovic Dedinje	Belgrade
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Dedinje Cardiovascular Institute	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Clinical Center Nis	Nis
Serbia	Niska Banja	Niska Banja
Serbia	Institute of Cardiovascular Diseases of Vojvodina	Sremska Kamenica
Slovakia	Stredoslovensky ustav srdcovych a cievnych chorob a s	Banska Bystrica
Slovakia	Alian s r o	Bardejov
Slovakia	Cardioconsult s r o	Bratislava
Slovakia	DIAMETABOL s r o	Bratislava
Slovakia	Veria s r o	Bratislava
Slovakia	Medicalgroup s r o	Kosice
Slovakia	KARDIO 1 s r o	Lucenec
Slovakia	Kardiologicka ambulancia Dr Kolikova	Povazska Bystrica
Slovakia	Medispol s r o	Presov
Slovakia	Interna SK s r o	Svidnik
Slovakia	MEDIVASA s r o	Zilina
Spain	Hospital Virgen del Mar	Almeria
Spain	Hospital del Mar	Barcelona
Spain	Hospital Quiron Barcelona	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda
Spain	Parc Sanitari Sant Joan de Deu	Sant Boi de Llobregat
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Nuestra Señora del Prado	Talavera de la Reina
Ukraine	Cherkasy Regional Cardiological Center	Cherkasy
Ukraine	CI Cherkasy RH of Cherkasy Regional Council	Cherkasy
Ukraine	Ivano-Frankivsk RCCD of MHU Dept of Arterial Hypertension SHEI Ivano-Frankivsk NMU	Ivano-Frankivsk
Ukraine	Ivano-Frankivsk Regional Clinical Cardiology Dispensary	Ivano-Frankivsk
Ukraine	CI of Healthcare Kharkiv CCH 8 Dept of Cardiology for Patients with MI 2 Kharkiv MA of PGE of MOHU	Kharkiv
Ukraine	GI L T Malaya Therapy National Institute of the NAMS of Ukraine	Kharkiv
Ukraine	Railway Transport Kharkiv CH#1 of Healthcare Center Branch of PJSC Ukrainian Railway	Kharkiv
Ukraine	SI Institute of General & Emergency Surgery of NAMS of Ukraine	Kharkiv
Ukraine	SMPI Central Clinical Hospital of Ukrzaliznytsia	Kharkiv
Ukraine	Kyiv CCH #12 Dept of Therapy O.O.Bogomolets NMU	Kyiv
Ukraine	Kyiv City Clinical Hospital 1	Kyiv
Ukraine	Med Center 'Ok!Clinic' of International Institute of Clinical Trials LLC	Kyiv
Ukraine	SI Heart Institute of the MoH of Ukraine	Kyiv
Ukraine	SI NS? M D Strazhesko Institute of Cardiology of NAMSU (9102)	Kyiv
Ukraine	SI NS? M D Strazhesko Institute of Cardiology of NAMSU (9116)	Kyiv
Ukraine	CI Lutsk CCH Volyn Regional Center of Cardiovascular Pathology and Thrombolysis	Luts'k
Ukraine	Regional State Clinical Treatment-Diagnostic Cardiological Centre	Lviv
Ukraine	CI Odesa Regional Clinical Hospital Regional Center of Cardiosurgery	Odesa
Ukraine	Multifield Medical Center of Odesa NMU (University Clinic 1)	Odesa
Ukraine	First CCH Cardiology Dept SHEIU Ukrainian Medical Stomatological Academy	Poltava
Ukraine	Transcarpathian RC Cardiology Dispensary Dept of General Cardiology SHEI Uzhgorod NU	Uzhgorod
Ukraine	M I Pyrogov VRCH M I Pyrogov VNMU Ch of IM 1	Vinnytsya
Ukraine	CI Zaporizhzhia Cl Hosp 10 Dept of Therapy SI ZMA of PGE of MoHU	Zaporizhzhya
Ukraine	CI Central City Hospital 2 of Zhytomyr	Zhytomyr
Ukraine	O F Herbachevskyi Regional Clinical Hospital of Zhytomyr RC	Zhytomyr

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.	Quintiles, Inc.

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Croatia,  Czechia,  Denmark,  Estonia,  Hungary,  Latvia,  Lithuania,  Poland,  Russian Federation,  Serbia,  Slovakia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics: Average Concentration of Edoxaban at Steady State (Cav)	In pharmacokinetics, steady state means the overall intake of a drug is about equal to its elimination	After initiation of dosing on Days 30, 90, and 360 (at pre dose, 1-2 hours post dose and 4-8 hours post-dose)
Primary	Pharmacokinetics: Minimum Concentration of Edoxaban in Plasma (Cmin)	Cmin is a term used in pharmacokinetics that usually refers to the minimum blood plasma concentration that a drug achieves after the drug has been administered and prior to the administration of a second dose	After initiation of dosing on Days 30, 90, and 360 (at pre dose, 1-2 hours post dose and 4-8 hours post-dose)
Primary	Pharmacodynamics: Mean exposure using validated assays	Exposure analysis performed with validated Liquid Chromatography/Tandem Mass Spectrometry/Mass Spectrometry (LC/MS/MS) assay with lithium heparin plasma.; Categories: Edoxaban and its metabolite (D21-2393)	Pre-dose and after initiation of dosing on Days 30, 90, and 360 (at pre dose, 1-2 hours post dose and 4-8 hours post-dose)
Primary	Pharmacodynamics: Mean exposure with anti-Factor Xa (FXa) assay	Exposure analysis performed with anti-FXa assay, using sodium citrate plasma samples Categories: Edoxaban and D21-2393	Pre-dose and after initiation of dosing on Days 30, 90, and 360 (at pre dose, 1-2 hours post dose and 4-8 hours post-dose)
Secondary	Efficacy: Number of participants with composite event 1	Composite event 1 includes ischemic or hemorrhagic stroke/transient ischemic attack (TIA) and systemic embolic events (SEE)	within 3 years
Secondary	Efficacy: Number of participants with composite event 2	Composite event 2 includes stroke/TIA, SEE, myocardial infarction, cardiovascular death, and major bleeding	within 3 years
Secondary	Safety: Number of participants with major bleeding (including intracranial)	Major bleeding is defined per the International Society on Thrombosis and Haemostasis (ISTH) definition	within 3 years
Secondary	Safety: Number of participants with clinically relevant bleeding	Clinically relevant bleeding is a combination of major bleeding and clinically relevant non-major (CRNM) bleeding	within 3 years
Secondary	Safety: Number of participants with any bleeding	Count of participants who experienced any bleeding event	within 3 years