Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation
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).
Interventions
DRUGPlacebo
Vernakalant (oral), 150 mg (b.i.d.) Vernakalant (oral), 300 mg (b.i.d.) Vernakalant (oral), 500 mg (b.i.d.)
Sponsors
Advanz Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| Improvement in QOL as measured by SF-36 | Improvement in QOL as measured by SF-36 within 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 |
| Time to first documented recurrence of symptomatic AF | Time to first documented recurrence of symptomatic AF within 90 days of dosing |
Countries
Australia, Belgium, Bulgaria, Croatia, Czechia, Denmark, Estonia, Germany, Hungary, Lithuania, Netherlands, New Zealand, Poland, Portugal, Romania, Russia, Serbia, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Ukraine
Outcome results
None listed