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

Advanz Pharma

Status and phase: Completed; Phase 2

Conditions: Atrial Fibrillation

Treatments: Drug: Vernakalant (oral); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00526136

1235-SR-202-AF

Details and patient eligibility

About

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).

Enrollment: 735 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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735 participants in 4 patient groups, including a placebo group

1

Placebo Comparator group

Description:

Placebo (b.i.d.)

Treatment:

Drug: Placebo

2

Experimental group

Description:

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

Treatment:

Drug: Vernakalant (oral)

3

Experimental group

Description:

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

Treatment:

Drug: Vernakalant (oral)

4

Experimental group

Description:

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

Treatment:

Drug: Vernakalant (oral)