vernakalant (oral) prevention of atrial fibrillation recurrence post-conversion study

Conditions: Atrial Fibrillation

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).


Eligibility criteria:
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+) \ 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;

Keywords: atrial fibrillation