Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study

To evaluate the safety, tolerability and efficacy of 3 doses of vernakalant (oral) (150 mg, 300 mg and 500 mg b.i.d.) administered for up to 90 days in subjects with sustained symptomatic atrial fibrillation (AF duration > 72 hours and < 6 months).

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Placebo; Drug: Vernakalant (oral)

• Study Type: Interventional
• Enrollment (Actual): 735
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Royal Adelaide Hospital
  • Hobart, Australia
    • Royal Hobart Hospital
  • Launceston, Australia
    • Launceston General Hospital
  • Woodville, Australia
    • Queen Elizabeth Hospital
  • Woolloongabba, Australia
    • Princess Alexandra Hospital
• Belgium
  • Antwerp, Belgium
    • A. Z. Middelheim
  • Bonheiden, Belgium
    • Imelda Ziekenhuis
  • Leuven, Belgium
    • U. Z. Gasthuisberg
  • Roeselare, Belgium
    • Heilig Hart Ziekenhuis
• Bulgaria
  • Haskovo, Bulgaria
    • MHAT - Haskovo
  • Pleven, Bulgaria
    • UMHAT 'Dr. Georgi Stranski'
  • Rousse, Bulgaria
    • MHAT 'Rouse AD'
  • Sofia, Bulgaria
    • Military Medical Academy
  • Sofia, Bulgaria
    • IV MHAT
  • Sofia, Bulgaria
    • MHAT 'Tzaritza Yoanna'
  • Sofia, Bulgaria
    • MI Central Clinical Base - Ministry of Interior
  • Varna, Bulgaria
    • MHAT 'Sveta Marina'
  • Varna, Bulgaria
    • MMA - Hospital Base for Active Treatment - Varna
• Croatia
  • Zadar, Croatia
    • General Hospital Zadar
  • Zagreb, Croatia
    • Clinical Hospital Dubrava
  • Zagreb, Croatia
    • General Hospital Sveti Duh
  • Zagreb, Croatia
    • University Hospital " Merkur "
• Czech Republic
  • Jindrichuv Hradec, Czech Republic
    • Nemocnice Jindrichuv Hradec, a.s.
  • Kromeriz, Czech Republic
    • Kromerizska Nemocnice, a.s.
  • Kutna Hora, Czech Republic
    • Nemocnice Kutna Hora s.r.o.
  • Plzen, Czech Republic
    • Fakultni nemocnice Plzen
  • Praha, Czech Republic
    • Vojenska Nemocnice Praha
  • Praha, Czech Republic
    • Vseobecna fakultni nemocnice v Praze
  • Pribram, Czech Republic
    • Oblastní nemocnice Příbram, a.s.
  • Semily, Czech Republic
    • Nemocnice v Semilech
  • Slany, Czech Republic
    • Nemocnice Slany
  • Tabor, Czech Republic
    • Nemocnice Tabor, a.s.
  • Trebic, Czech Republic
    • Nemocnice Trebic, p.o.
• Denmark
  • Copenhagen, Denmark
    • Bispebjerg Hospital
  • Frederiksberg, Denmark
    • Frederiksberg Hospital
  • Hellerup, Denmark
    • Gentofte Amtssygehus
  • Hjorring, Denmark
    • Sygehus Vendsyssel - Hjørring
  • Koge, Denmark
    • Region Sjælland Sygehus øst Køge
  • Kolding, Denmark
    • Kolding Sygehus
• Estonia
  • Haabneeme, Estonia
    • Viimsi Hospital
  • Parnu, Estonia
    • Parnu Hospital
  • Tallinn, Estonia
    • North Estonia Regional Hospital
  • Tartu, Estonia
    • Tartu University Hospital
• Germany
  • Bad Krozingen, Germany
    • Herzzentrum Bad Krozingen
  • Bad Nauheim, Germany
    • Kerckhoff-Klinik Forschungsgesellschaft mbH
  • Witten, Germany
    • Evangelisches Krankenhaus
• Hungary
  • Ajka, Hungary
    • Magyar Imre Hospital
  • Baja, Hungary
    • Baja City Community Hospital
  • Budapest, Hungary
    • Nyiro Gyula Hospital
  • Budapest, Hungary
    • Péterfy Sándor Hospital
  • Budapest, Hungary
    • Szent Istvan Hospital
  • Gyongyos, Hungary
    • Bugat Pal Hospital
  • Gyor, Hungary
    • Petz Aladar County Teaching Hospital
  • Kecskemet, Hungary
    • Bács-Kiskun County Hospital
  • Szekesfehervar, Hungary
    • Fejer Megyei Szent Gyorgy Korhaz
  • Szolnok, Hungary
    • Hetenyi Geza County Hospital
  • Zalaegerszeg, Hungary
    • Zala County Hospital
• Lithuania
  • Kaunas, Lithuania
    • Kaunas Medical University Hospital
  • Klaipeda, Lithuania
    • Klaipeda Seamen's Hospital
  • Vilnius, Lithuania
    • Vilnius University Hospital Santariskiu Clinic
• Netherlands
  • Amsterdam, Netherlands
    • VU Medisch Centrum
  • Delft, Netherlands
    • Reinier de Graaf Groep
  • Eindhoven, Netherlands
    • Catharina Ziekenhuis
  • Groningen, Netherlands
    • Martini Ziekenhuis
  • Maastricht, Netherlands
    • Academisch Ziekenhuis Maastricht
  • Nieuwegein, Netherlands
    • Stichting Sint Antonius Ziekenhuis
  • Zwolle, Netherlands
    • Isala Klinieken
• New Zealand
  • Auckland, New Zealand
    • North Shore Hospital
  • Dunedin, New Zealand
    • Dunedin Hospital
  • Hamilton, New Zealand
    • Waikato Hospital
  • Nelson, New Zealand
    • Nelson Hospital
• Poland
  • Bydgoszcz, Poland
    • SZZOZ Wielospecjalityczny Szpital Miejski im. Dr. E.Warminsk
  • Chrzanow, Poland
    • Szpital Powiatowy
  • Gdansk, Poland
    • Instytut Kardiologii AMG
  • Gdynia, Poland
    • Szpital Miejski w Gdyni
  • Lodz, Poland
    • Zaklad Farmakologii i Terapii Monitorowanej z Oddzialem Chor
  • Lublin, Poland
    • SP ZOZ Okregowy Szpital Kolejowy
  • Rzeszow, Poland
    • Szpital Wojewodzki Nr 2
  • Szczecin, Poland
    • Klinika Kardiologii PAM
  • Tarnow, Poland
    • Szpital Specjalistyczny
  • Warsaw, Poland
    • III Klinika Chorob Wewnetrznych i Kardiologii
  • Warsaw, Poland
    • Wojskowy Instytut Medyczny, CSK MON
  • Wroclaw, Poland
    • Osrodek Chorob Serca, 4Wojskowy Szpital Kliniczny z Poliklin
• Portugal
  • Amadora, Portugal
    • Hospital Fernando da Fonseca
  • Lisbon, Portugal
    • Hospital De Santa Marta
  • Vila Nova de Gaia, Portugal
    • Centro Hospitalar Vila Nova de Gaia
• Romania
  • Arad, Romania
    • Spitalul Clinic Judetean de Urgenta Arad
  • Brasov, Romania
    • Spitalul Clinic Judetean de Urgenta Brasov
  • Bucuresti, Romania
    • Institutul de Cardiologie C.C. Iliescu
  • Bucuresti, Romania
    • Spitalul Clinic Colentina
  • Bucuresti, Romania
    • Spitalul Clinic de Urgenta Sf. Pantelimon
  • Lasi, Romania
    • Spitalul Clinic Judetean de Urgenta Sf. Spiridon Iasi
  • Oradea, Romania
    • Spitalul Clinic Judetean Oradea
  • Ploiesti, Romania
    • Spitalul Judetean de Urgenta Ploiesti
  • Targu Mures, Romania
    • Spitalul Clinic Judetean de Urgenta Targu Mures
  • Timisoara, Romania
    • Spitalul Clinic Municipal de Urgenta Timisoara
• Russian Federation
  • Moscow, Russian Federation
    • FSI EMC of the President of RF, b.o. City Hospital #51
  • Moscow, Russian Federation
    • MedCentre of RF President, Central Clinical Hospital
  • Moscow, Russian Federation
    • Moscow City Hospital # 29
  • Moscow, Russian Federation
    • Moscow Medical Academy. City Hospital #20
  • Moscow, Russian Federation
    • Moscow SHI City Clinical Hospital #52
  • Moscow, Russian Federation
    • RMA of Postg. education b.o. Botkin City Clinical Hospital
  • Moscow, Russian Federation
    • Russian Cardiology Research Centre
  • Moscow, Russian Federation
    • War Veteran's Hospital #3
  • St Petersburg, Russian Federation
    • Pokrovskaya City Hospital
  • St Petersburg, Russian Federation
    • St- Petersburg GUZ City Hospital #15
  • Yaroslavl, Russian Federation
    • Yaroslavl Regional Clinical Hospital
  • Yaroslavl, Russian Federation
    • Yaroslavl State Medical Academy b.o. Clinical Hospital #2
• Serbia
  • Belgrade, Serbia
    • Clinical Center of Serbia
  • Belgrade, Serbia
    • Dedinje Cardiovascular Institute
  • Belgrade, Serbia
    • Institute of CV Diseases, Clinical Center of Serbia
  • Niska Banja, Serbia
    • Clinical Center for Cardiovascular Diseases
  • Sremska Kamenica, Serbia
    • Institute of Cardiovascular Diseases Sremska Kamenica
  • Zemun, Serbia
    • Clinical Center Bezanijska Kosa
  • Zemun, Serbia
    • Clinical Center Zemun
• Singapore
  • Singapore, Singapore
    • National Heart Center
• Slovakia
  • Bratislava, Slovakia
    • FNsP Bratislava - Pracovisko Stare Mesto
  • Bratislava, Slovakia
    • Slovensky Ustav Srdcovocievnych Chorob
  • Kosice, Slovakia
    • Vychodoslovensky Ustav Srdcovocievnych Chorob
  • Nitra, Slovakia
    • Fakultná nemocnica Nitra
  • Nove Zamky, Slovakia
    • FNsP Nove Zamky
  • Presov, Slovakia
    • FNsP J. A. Reimana
• South Africa
  • Kempton Park, South Africa
    • Clinresco Centres (Pty) Ltd
  • Somerset West, South Africa
    • Vergelegen Medi-Clinic
  • Worcester, South Africa
    • Clinical Project Research
• Spain
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Granada, Spain
    • Hosp. Virgen de las Nieves
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Clinica Universitaria Puerta de Hierro
  • Madrid, Spain
    • Hosp. Clinico San Carlos
  • Tarragona, Spain
    • Hospital Univ. Tarragona Joan XXIII
• Sweden
  • Malmo, Sweden
    • Universitetssjukhuset Malmö
  • Orebro, Sweden
    • Universitetssjukhuset Orebro
  • Uppsala, Sweden
    • Akademiska Sjukhuset
• Switzerland
  • Basel, Switzerland
    • Universitaetsspital Basel
  • Liestal, Switzerland
    • Kantonsspital Liestal
  • Lugano, Switzerland
    • Cardio Centro Ticino
  • St Gallen, Switzerland
    • Kantonsspital St. Gallen
• Ukraine
  • Dnepropetrovsk, Ukraine
    • Reg.Diag.Center of Dnepr.
  • Donetsk, Ukraine
    • Cent.City Clin.Hosp.#3.Chair of Int.Dis.#2 of Donetsk SMU
  • Donetsk, Ukraine
    • Donetsk Regional Clinical Hospital
  • Kharkov, Ukraine
    • City Clinical Hospital #8
  • Kiev, Ukraine
    • City Clinical Hospital #1
  • Kiev, Ukraine
    • Kiev City Clinical Hospital No 5, Coronary Care Unit
  • Kiev, Ukraine
    • Kiev Clinical Emergency Care Hospital
  • Kiev, Ukraine
    • M.D.Strazhesko Institut of Cardiology
  • Kiev, Ukraine
    • N.D. Strazhesko Institute of Cardiology
  • Lugansk, Ukraine
    • Lugansk First Clinical Multiprofile Hospital #1, Cardiology
  • Lviv, Ukraine
    • Lviv Reg St Clinical Treat-and-Diagn Cardio. Centre
  • Odessa, Ukraine
    • City Clinical Hospital #9
  • Zaporizhzhya, Ukraine
    • Hospital Therapy Dept #1of Zaporozhye SMU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Comprehend and sign a written informed consent form, (per local and national regulations, as applicable)
• Be 18 to 85 years of age
• Women must not be pregnant, be non-nursing and if pre-menopausal, must be using an effective form of birth control from time of screening until 3 months after the last dose of medication. Methods of birth control considered to be effective may include hormonal contraception (the pill), an intrauterine device (IUD), condoms in combination with a spermicidal cream, total abstinence or sterilisation. Men should be advised not to conceive a child and are advised to use an effective form of birth control from admission until 3 months after the last dose of study medication
• Have symptomatic AF that has been sustained for greater than 72 hours and less than 6 months duration and is clinically indicated for cardioversion;
• Have adequate anticoagulant therapy for cardioversion in accordance with standard of practice as recommended by ACC/AHA/ESC guidelines (Fuster V. et al, 2006);
• Be haemodynamically stable (100 mmHg < systolic blood pressure < 190 mmHg) at screening and on Day 1 before dosing (while taking rate control drugs, if required). After resting supine for 3 minutes, blood pressures should be measured 3 times in 5 minutes with at least 1 minute between assessments;
• Have a body weight between 45 and 113 kg (99 and 250 lbs).

Exclusion Criteria:

• Have known prolonged QT syndrome or QTcB interval of >0.500 sec as measured at screening on a 12 lead ECG; familial long QT syndrome; previous Torsades de Pointes; ventricular fibrillation; or sustained ventricular tachycardia (VT).
• Have a QRS >0.140 sec;
• Documented previous episodes of second or third-degree atrioventricular block;
• Have clinically significant persistent bradycardia with ventricular rate below 50 beats/min, sick-sinus syndrome or pacemaker;
• Have clinically significant moderate or severe aortic valvular stenosis (gradient >25 mmHg), hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis;
• Have Class III or Class IV congestive heart failure at screening or admission, or have been hospitalized for heart failure in the previous 6 months;
• Have a myocardial infarction (MI), cardiac surgery, angioplasty, unstable angina or acute coronary syndrome within 30 days prior to entry into the study; h) Have serious pulmonary, hepatic, metabolic, renal (serum creatinine > 2.0 mg/dl), gastrointestinal, central nervous system (CNS) or psychiatric disease, end-stage disease states, or any other disease that could interfere with the conduct or validity of the study or compromise subject safety;
• Have known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, pneumonia, hypoxemia (oxygen saturation < 90% on room air), acute pericarditis, or myocarditis;
• Potassium (K+) <3.5 mmol/L or >5.5 mmol/L or magnesium (Mg2+) below the lower limit of normal (Mg2+< 0.65 mmol/L in subjects 65 years or younger and <0.80 mmol/L in subjects 66 years or older). (Both K+ and Mg2+ should be corrected prior to dosing);
• Have clinical evidence of digoxin toxicity;
• Have received an oral Class I or Class III antiarrhythmic agent (including sotalol) within 3 days of randomisation or oral amiodarone within 4 weeks, or have received intravenous Class I or Class III antiarrhythmic agent or i.v. amiodarone within 24 hours prior to start of dosing;
• Have any other surgical or medical condition that, in the judgment of the clinical Investigator might warrant exclusion or be contraindicated for safety reasons;
• Be concurrently participating in another drug study or have received an investigational drug within 30 days prior to screening;
• Be unable to communicate well with the Investigator and to comply with the requirements of the entire study;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1; Placebo (b.i.d.)	Drug: Placebo
Experimental: 2; Vernakalant (oral), 150 mg (b.i.d.)	Drug: Vernakalant (oral); Vernakalant (oral), 150 mg (b.i.d.) Vernakalant (oral), 300 mg (b.i.d.) Vernakalant (oral), 500 mg (b.i.d.); Other Names: RSD1235-SR
Experimental: 3; Vernakalant (oral), 300 mg (b.i.d.)	Drug: Vernakalant (oral); Vernakalant (oral), 150 mg (b.i.d.) Vernakalant (oral), 300 mg (b.i.d.) Vernakalant (oral), 500 mg (b.i.d.); Other Names: RSD1235-SR
Experimental: 4; Vernakalant (oral), 500 mg (b.i.d.)	Drug: Vernakalant (oral); Vernakalant (oral), 150 mg (b.i.d.) Vernakalant (oral), 300 mg (b.i.d.) Vernakalant (oral), 500 mg (b.i.d.); Other Names: RSD1235-SR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to first documented recurrence of symptomatic sustained AF.	Time to first documented recurrence of symptomatic sustained AF within Day 90 of dosing
Safety assessments- Vital signs, safety laboratory assays, ECG parameters, physical examinations, and frequency of adverse events	Safety assessments within Day 120 of dosing

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to first documented recurrence of symptomatic or asymptomatic sustained AF	Time to first documented recurrence of symptomatic or asymptomatic sustained AF within 90 days of dosing
Time to first documented recurrence of symptomatic AF	Time to first documented recurrence of symptomatic AF within 90 days of dosing
Time to first documented recurrence of symptomatic or asymptomatic AF	Time to first documented recurrence of symptomatic or asymptomatic AF within 90 days of dosing
Proportion of subjects in sinus rhythm on Day 90.	Proportion of subjects in sinus rhythm on Day 90 of dosing
Improvement in AF symptoms as assessed by an AF symptom checklist.	Improvement in AF symptoms as assessed by an AF symptom checklist within Day 90 of dosing
Improvement in QOL as measured by SF-36	Improvement in QOL as measured by SF-36 within Day 90 of dosing

Collaborators and Investigators

• Sponsor: Advanz Pharma
• Investigators: Study Director: Gregory Beatch, PhD, Advanz Pharma

Publications and helpful links

General Publications

• Torp-Pedersen C, Raev DH, Dickinson G, Butterfield NN, Mangal B, Beatch GN. A randomized, placebo-controlled study of vernakalant (oral) for the prevention of atrial fibrillation recurrence after cardioversion. Circ Arrhythm Electrophysiol. 2011 Oct;4(5):637-43. doi: 10.1161/CIRCEP.111.962340. Epub 2011 Aug 14.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: September 5, 2007
• First Submitted That Met QC Criteria: September 6, 2007
• First Posted (Estimate): September 10, 2007

Study Record Updates

• Last Update Posted (Estimate): December 18, 2008
• Last Update Submitted That Met QC Criteria: December 17, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: Atrial Fibrillation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Arrhythmias, Cardiac; Atrial Fibrillation; Recurrence
• Other Study ID Numbers: 1235-SR-202-AF