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

NCT00526136 | Completed Phase 2

• 1 other identifier: 1235-SR-202-AF
• Study Type: interventional
• Target: 735
• Locations: 22 countries
• Sites: 138

Brief Summary

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).

Conditions

Atrial Fibrillation

Keywords

Atrial Fibrillation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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

Study Arms (4)

1

PLACEBO COMPARATOR

Placebo (b.i.d.)

Drug: Placebo

2

EXPERIMENTAL

Vernakalant (oral), 150 mg (b.i.d.)

Drug: Vernakalant (oral)

3

EXPERIMENTAL

Vernakalant (oral), 300 mg (b.i.d.)

Drug: Vernakalant (oral)

4

EXPERIMENTAL

Vernakalant (oral), 500 mg (b.i.d.)

Drug: Vernakalant (oral)

Interventions

Placebo DRUG

1

Vernakalant (oral) DRUG

Vernakalant (oral), 150 mg (b.i.d.) Vernakalant (oral), 300 mg (b.i.d.) Vernakalant (oral), 500 mg (b.i.d.)

Also known as: RSD1235-SR

2; 3; 4

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Advanz Pharma: lead

Study Sites (152)

Royal Adelaide Hospital

Adelaide, Australia

Location

Royal Hobart Hospital

Hobart, Australia

Location

Launceston General Hospital

Launceston, Australia

Location

Queen Elizabeth Hospital

Woodville, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Australia

Location

A. Z. Middelheim

Antwerp, Belgium

Location

Imelda Ziekenhuis

Bonheiden, Belgium

Location

U. Z. Gasthuisberg

Leuven, Belgium

Location

Heilig Hart Ziekenhuis

Roeselare, Belgium

Location

MHAT - Haskovo

Haskovo, Bulgaria

Location

UMHAT 'Dr. Georgi Stranski'

Pleven, Bulgaria

Location

MHAT 'Rouse AD'

Rousse, Bulgaria

Location

IV MHAT

Sofia, Bulgaria

Location

MHAT 'Tzaritza Yoanna'

Sofia, Bulgaria

Location

MI Central Clinical Base - Ministry of Interior

Sofia, Bulgaria

Location

Military Medical Academy

Sofia, Bulgaria

Location

MHAT 'Sveta Marina'

Varna, Bulgaria

Location

MMA - Hospital Base for Active Treatment - Varna

Varna, Bulgaria

Location

General Hospital Zadar

Zadar, Croatia

Location

Clinical Hospital Dubrava

Zagreb, Croatia

Location

General Hospital Sveti Duh

Zagreb, Croatia

Location

University Hospital " Merkur "

Zagreb, Croatia

Location

Nemocnice Jindrichuv Hradec, a.s.

Jindřichův Hradec, Czechia

Location

Kromerizska Nemocnice, a.s.

Kroměříž, Czechia

Location

Nemocnice Kutna Hora s.r.o.

Kutná Hora, Czechia

Location

Fakultni Nemocnice Plzen

Pilsen, Czechia

Location

Vojenska Nemocnice Praha

Prague, Czechia

Location

Vseobecna Fakultni Nemocnice v Praze

Prague, Czechia

Location

Oblastni Nemocnice Pribram, a.s.

Příbram, Czechia

Location

Nemocnice v Semilech

Semily, Czechia

Location

Nemocnice Slany

Slaný, Czechia

Location

Nemocnice Tabor, a.s.

Tábor, Czechia

Location

Nemocnice Trebic, p.o.

Třebíč, Czechia

Location

Bispebjerg Hospital

Copenhagen, Denmark

Location

Frederiksberg Hospital

Frederiksberg, Denmark

Location

Gentofte Amtssygehus

Hellerup, Denmark

Location

Sygehus Vendsyssel - Hjørring

Hjørring, Denmark

Location

Kolding Sygehus

Kolding, Denmark

Location

Region Sjælland Sygehus øst Køge

Køge, Denmark

Location

Viimsi Hospital

Haabneeme, Estonia

Location

Pärnu Hospital

Pärnu, Estonia

Location

North Estonia Regional Hospital

Tallinn, Estonia

Location

Tartu University Hospital

Tartu, Estonia

Location

Herzzentrum Bad Krozingen

Bad Krozingen, Germany

Location

Kerckhoff-Klinik Forschungsgesellschaft mbH

Bad Nauheim, Germany

Location

Evangelisches Krankenhaus

Witten, Germany

Location

Magyar Imre Hospital

Ajka, Hungary

Location

Baja City Community Hospital

Baja, Hungary

Location

Nyiro Gyula Hospital

Budapest, Hungary

Location

Péterfy Sándor Hospital

Budapest, Hungary

Location

Szent Istvan Hospital

Budapest, Hungary

Location

Bugat Pal Hospital

Gyöngyös, Hungary

Location

Petz Aladár County Teaching Hospital

Győr, Hungary

Location

Bacs-Kiskun County Hospital

Kecskemét, Hungary

Location

Fejér Megyei Szent György Kórház

Székesfehérvár, Hungary

Location

Hetenyi Geza County Hospital

Szolnok, Hungary

Location

Zala County Hospital

Zalaegerszeg, Hungary

Location

Kaunas Medical University Hospital

Kaunas, Lithuania

Location

Klaipeda Seamen's Hospital

Klaipėda, Lithuania

Location

Vilnius University Hospital Santariskiu Clinic

Vilnius, Lithuania

Location

VU Medisch Centrum

Amsterdam, Netherlands

Location

Reinier de Graaf Groep

Delft, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, Netherlands

Location

Martini Ziekenhuis

Groningen, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, Netherlands

Location

Stichting Sint Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Isala Klinieken

Zwolle, Netherlands

Location

North Shore Hospital

Auckland, New Zealand

Location

Dunedin Hospital

Dunedin, New Zealand

Location

Waikato Hospital

Hamilton, New Zealand

Location

Nelson Hospital

Nelson, New Zealand

Location

SZZOZ Wielospecjalityczny Szpital Miejski im. Dr. E.Warminsk

Bydgoszcz, Poland

Location

Szpital Powiatowy

Chrzanów, Poland

Location

Instytut Kardiologii AMG

Gdansk, Poland

Location

Szpital Miejski w Gdyni

Gdynia, Poland

Location

Zaklad Farmakologii i Terapii Monitorowanej z Oddzialem Chor

Lodz, Poland

Location

SP ZOZ Okregowy Szpital Kolejowy

Lublin, Poland

Location

Szpital Wojewodzki Nr 2

Rzeszów, Poland

Location

Klinika Kardiologii PAM

Szczecin, Poland

Location

Szpital Specjalistyczny

Tarnów, Poland

Location

III Klinika Chorob Wewnetrznych i Kardiologii

Warsaw, Poland

Location

Wojskowy Instytut Medyczny, CSK MON

Warsaw, Poland

Location

Osrodek Chorob Serca, 4Wojskowy Szpital Kliniczny z Poliklin

Wroclaw, Poland

Location

Hospital Fernando da Fonseca

Amadora, Portugal

Location

Hospital de Santa Marta

Lisbon, Portugal

Location

Centro Hospitalar Vila Nova de Gaia

Vila Nova de Gaia, Portugal

Location

Spitalul Clinic Judetean de Urgenta Arad

Arad, Romania

Location

Spitalul Clinic Judetean de Urgenta Brasov

Brasov, Romania

Location

Institutul de Cardiologie C.C. Iliescu

Bucharest, Romania

Location

Spitalul Clinic Colentina

Bucharest, Romania

Location

Spitalul Clinic de Urgenta Sf. Pantelimon

Bucharest, Romania

Location

Spitalul Clinic Judetean de Urgenta Sf. Spiridon Iasi

Lasi, Romania

Location

Spitalul Clinic Judetean Oradea

Oradea, Romania

Location

Spitalul Judetean de Urgenta Ploiesti

Ploieşti, Romania

Location

Spitalul Clinic Judetean de Urgenta Targu Mures

Târgu Mureş, Romania

Location

Spitalul Clinic Municipal de Urgenta Timisoara

Timișoara, Romania

Location

FSI EMC of the President of RF, b.o. City Hospital #51

Moscow, Russia

Location

MedCentre of RF President, Central Clinical Hospital

Moscow, Russia

Location

Moscow City Hospital # 29

Moscow, Russia

Location

Moscow Medical Academy. City Hospital #20

Moscow, Russia

Location

Moscow SHI City Clinical Hospital #52

Moscow, Russia

Location

RMA of Postg. education b.o. Botkin City Clinical Hospital

Moscow, Russia

Location

Russian Cardiology Research Centre

Moscow, Russia

Location

War Veteran's Hospital #3

Moscow, Russia

Location

Pokrovskaya City Hospital

Saint Petersburg, Russia

Location

St- Petersburg GUZ City Hospital #15

Saint Petersburg, Russia

Location

Yaroslavl Regional Clinical Hospital

Yaroslavl, Russia

Location

Yaroslavl State Medical Academy b.o. Clinical Hospital #2

Yaroslavl, Russia

Location

Clinical Center of Serbia

Belgrade, Serbia

Location

Dedinje Cardiovascular Institute

Belgrade, Serbia

Location

Institute of CV Diseases, Clinical Center of Serbia

Belgrade, Serbia

Location

Institute of Cardiovascular Diseases Sremska Kamenica

Kamenitz, Serbia

Location

Clinical Center for Cardiovascular Diseases

Niška Banja, Serbia

Location

Clinical Center Bezanijska Kosa

Zemun, Serbia

Location

Clinical Center Zemun

Zemun, Serbia

Location

National Heart Center

Singapore, Singapore

Location

FNsP Bratislava - Pracovisko Stare Mesto

Bratislava, Slovakia

Location

Slovensky Ustav Srdcovocievnych Chorob

Bratislava, Slovakia

Location

Vychodoslovensky Ustav Srdcovocievnych Chorob

Košice, Slovakia

Location

Fakultna Nemocnica Nitra

Nitra, Slovakia

Location

FNsP Nove Zamky

Nové Zámky, Slovakia

Location

FNsP J. A. Reimana

Prešov, Slovakia

Location

Clinresco Centres (Pty) Ltd

Kempton Park, South Africa

Location

Vergelegen Medi-Clinic

Somerset West, South Africa

Location

Clinical Project Research

Worcester, South Africa

Location

Hospital Vall D'Hebron

Barcelona, Spain

Location

Hosp. Virgen de las Nieves

Granada, Spain

Location

Clinica Universitaria Puerta de Hierro

Madrid, Spain

Location

Hosp. Clinico San Carlos

Madrid, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Univ. Tarragona Joan XXIII

Tarragona, Spain

Location

Universitetssjukhuset Malmö

Malmo, Sweden

Location

Universitetssjukhuset Örebro

Örebro, Sweden

Location

Akademiska Sjukhuset

Uppsala, Sweden

Location

Universitaetsspital Basel

Basel, Switzerland

Location

Kantonsspital Liestal

Liestal, Switzerland

Location

Cardio Centro Ticino

Lugano, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

Location

Reg.Diag.Center of Dnepr.

Dnipro, Ukraine

Location

Cent.City Clin.Hosp.#3.Chair of Int.Dis.#2 of Donetsk SMU

Donetsk, Ukraine

Location

Donetsk Regional Clinical Hospital

Donetsk, Ukraine

Location

City Clinical Hospital #8

Kharkiv, Ukraine

Location

City Clinical Hospital #1

Kiev, Ukraine

Location

Kiev City Clinical Hospital No 5, Coronary Care Unit

Kiev, Ukraine

Location

Kiev Clinical Emergency Care Hospital

Kiev, Ukraine

Location

M.D.Strazhesko Institut of Cardiology

Kiev, Ukraine

Location

N.D. Strazhesko Institute of Cardiology

Kiev, Ukraine

Location

Lugansk First Clinical Multiprofile Hospital #1, cardiology

Luhansk, Ukraine

Location

Lviv Reg St Clinical Treat-and-Diagn Cardio. Centre

Lviv, Ukraine

Location

City Clinical Hospital #9

Odesa, Ukraine

Location

Hospital Therapy Dept #1of Zaporozhye SMU

Zaporizhzhya, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 21841207 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

vernakalant

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gregory Beatch, PhD

  Advanz Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 5, 2007
• First Posted: September 10, 2007
• Study Start: March 1, 2007
• Study Completion: July 1, 2008
• Last Updated: December 18, 2008

Record last verified: 2008-12

Locations

DE (3); BE (4); RO (10); RU (12); UA (13); CZ (11); CR (4); HU (11); PL (12); BU (9); SE (3); DK (6); LI (3); NL (7); SL (6); ES (4); CH (4); ZA (3); PT (3); AU (5); NZ (4); SG (1)