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

Study Overview
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Brief Summary
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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).

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

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Placebo
* Drug: Vernakalant (oral)


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation