Recent Onset Symptomatic Atrial Fibrillation MedDRA version: 20.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: Vernakalant
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vernakalant Hydrochloride
CAS Number: 748810-28-8
Current Sponsor code: KSD1235
Other descriptive name: Verna
Sponsors
Cardiome UK Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject is eligible for the study if all of the following apply: 1. Institutional Review board (IRB)-/Independent Ethics Committee (IEC)- approved written Informed Consent and privacy language as per national regulations (e.g. HIPAA Authorization for U.S. sites) must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable); 2. Subject must be between the ages of 18 and 85, inclusive; 3. Females must be not pregnant or nursing and if pre-menopausal, must be using an effective form of birth control from time of screening until 30 days post study treatment; 4. Subject must have recent onset (> 3 hours to less than or equal to 7 days) symptomatic AF determined by the Investigator to be best managed by acute conversion to SR. The presence of atrial fibrillation will be documented by a 12-lead ECG recording at Screening and Baseline; 5. Subject must have, in the judgment of the Investigator, adequate anticoagulant therapy (AF has lasted more than 48 hours, subjects should be managed in accordance with standard of practice as recommended by ACC/AHA/ESC practice guidelines) 6. Subject must have systolic blood pressure (SBP) above 90 mmHg and less than 160 mmHg and diastolic blood pressure (DBP) less than 95 mmHg at Screening (single measurement) and Baseline (mean of triplicate measurements); 7. Subject must be, in the judgment of the Investigator, adequately hydrated and have a normal saline IV established and infusing; 8. Subject must have a body weight between 45 and 136 kg, inclusive (99 and 300 lbs). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subject will be excluded from participation if any of the following apply: 1. Subject has a history of heart failure or documentation of left ventricular dysfunction evidenced by any of the following: a- History of heart failure defined as physician documentation or report of any of the following symptoms of heart failure before this care encounter, described as dyspnea, fluid retention, and/or low cardiac output secondary to cardiac dysfunction; or the description of rales, jugular venous distension, or pulmonary edema. A previous hospital admission with diagnosis of heart failure is considered evidence of heart failure history b- Objective evidence of heart failure during the present care encounter with documentation of rales, jugular venous distension, or pulmonary edema. c- Left ventricular dysfunction defined as an ejection fraction of less than 40%, if available. An echocardiogram is not required for enrollment in this study. 2. Subject has known or suspected prolonged QT or uncorrected QT interval of > 0.440 sec. as measured at Screening on a 12-lead ECG, familial long QT syndrome, or previous Torsade de Pointes; 3. Subject has symptomatic bradycardia or ventricular rate less than 50 bpm documented by 12-lead ECG at Screening, unless controlled by a pacemaker; 4. Subject has bradycardia (heart rate less than 50 bpm) or hypotension (SBP less that 90 mmHg) after receiving a loading, bolus dose, or sustained infusion of any rate control medication during Screening; 5. Subject has a QRS interval > 0.14 sec., unless subject has a pacemaker; 6. Subject had a myocardial infarction (MI), acute coronary syndrome, cardiac surgery (including PTCA or stent placement), within 30 days prior to enrollment or subject has evidence of new ischemic changes on Screening 12-lead ECG; 7. Subject has troponin I or T levels beyond the upper limit of normal for the local lab at Screening; 8. Subject has significant valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis; 9. Subject has failed electrical cardioversion for AF at anytime; 10. Subject has failed pharmacologic conversion with an intravenous Class I or Class III antiarrhythmic drug for this episode of AF; 11. Subject has any known reversible causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, acute pericarditis or hypoxemia (oxygen saturation less than 90% of room air); 12. Subject has uncorrected electrolyte imbalance (serum potassium less than 3.5 mmol/L must be corrected and documented 6 hours or less prior to enrollment, hypomagnesemia of any level is an exclusion); 13. Subject has clinical evidence of digoxin toxicity in the opinion of the Investigator; 14. Subject has a history of clinically significant illness (e.g. neurological, gastrointestinal, renal, hepatic, pulmonary, metabolic, endocrine, hematological, or psychiatric), medical condition or laboratory abnormality within 4 weeks prior to Screening, that in the Investigator’s opinion, would preclude the subject from participating in the trial; 15. Subject is unable to communicate well with the Investigator and to comply with the requirements of the entire study; 16. Subject has previously participated in a vernakalant study, is concurrently participating in another drug study, or has received an investigational drug within 30 days prior to Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary safety objective of this study is to evaluate the safety of vernakalant injection in subjects with recent onset (AF > 3 hours to less than or equal to 7 days), symptomatic atrial fibrillation, and no evidence or history of congestive heart failure (CHF). The primary efficacy objective is to demonstrate the efficacy of vernakalant injection in converting atrial fibrillation (AF) to sinus rhythm (SR) in subjects with recent onset (AF > 3h to less than or equal to 7 days), symptomatic atrial fibrillation and no evidence or history of congestive heart failure (CHF).;Secondary Objective: The study will evaluate the influence of CYP2D6 genotype status on the pharmacokinetics and pharmacodynamics of vernakalant (and its metabolites). Additionally, the study allows for an exploratory analysis of safety and healthcare resource utilization between vernakalant and electrocardioversion (ECV).;Primary end point(s): Using a two-sided chi-square test with a significance level of 0.05, this sample size will provide more than 98% power to detect a treatment difference of 35% in the primary efficacy endpoint of conversion of AF to sinus rhythm between the two treatment groups assuming the placebo conversion rate is 10%. The primary analysis will use subjects in the safety analysis set (SAF) from the vernakalant group only. A one-sided 95% confidence interval using the Exact method for a single proportion will be used to provide an interval estimate of the incidence for the primary composite safety endpoint. In addition, the placebo group will be summarized using the same methodology. A subject is considered success for this exploratory efficacy endpoint if the subject converted to SR as defined in the primary efficacy variable and maintained SR documented by Holter or by two consecutive 12-lead ECGs recorded > 1 minute apart at 24 +/minus 4 hours. | — |
Countries
Belgium
Contacts
Public ContactCéline Combet
Cardiome UK Ltd
Outcome results
None listed