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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00526136
• Date of registration: 05/09/2007
• Prospective Registration: No
• Primary sponsor: Cardiome Pharma
• Public title: Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study
• Scientific title: Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study
• Date of first enrolment: March 2007
• Target sample size: 735
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00526136
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
• Phase: Phase 2

Countries of recruitment

Australia, Belgium, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Former Serbia and Montenegro, Germany, Hungary, Lithuania, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Ukraine

Contacts

• Name: Gregory Beatch, PhD
• Affiliation: Cardiome Pharma

Key inclusion & exclusion 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+) <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;



Age minimum: 18 Years
Age maximum: 85 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Atrial Fibrillation

Intervention(s)

Drug: Placebo

Drug: Vernakalant (oral)

Primary Outcome(s)

Time to first documented recurrence of symptomatic sustained AF. [Time Frame: 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 [Time Frame: Safety assessments within Day 120 of dosing]

Secondary Outcome(s)

Proportion of subjects in sinus rhythm on Day 90. [Time Frame: Proportion of subjects in sinus rhythm on Day 90 of dosing]

Improvement in QOL as measured by SF-36 [Time Frame: Improvement in QOL as measured by SF-36 within Day 90 of dosing]

Time to first documented recurrence of symptomatic or asymptomatic AF [Time Frame: Time to first documented recurrence of symptomatic or asymptomatic AF within 90 days of dosing]

Improvement in AF symptoms as assessed by an AF symptom checklist. [Time Frame: 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 Frame: Time to first documented recurrence of symptomatic AF within 90 days of dosing]

Time to first documented recurrence of symptomatic or asymptomatic sustained AF [Time Frame: Time to first documented recurrence of symptomatic or asymptomatic sustained AF within 90 days of dosing]

Secondary ID(s)

1235-SR-202-AF

Source(s) of Monetary Support

Please refer to primary and secondary sponsors