A Phase III Prospective, Randomized, Double-Blind, Active-Controlled, Multi-Center, Superiority Study of Vernakalant Injection versus Amiodarone in Subjects with Recent Onset Atrial Fibrillatio

Phase 3

Completed

Conditions: atrial fibrillation (AF)
10007593
irregular heart-rhythm
10007521

Registration Number: NL-OMON33298

Lead Sponsor: Quintiles

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 16

Inclusion Criteria

1. Have symptomatic AF of 3 to 48 hours duration at baseline.
2. Be eligible for cardioversion.
3. Be 18 to 85 years of age.
4. Comprehend and sign a written informed consent form.
5. 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 discharge.
6. Have adequate anticoagulation therapy for cardioversion in accordance with standard of practice as recommended by ACC/AHA/ESC guidelines [1].
7. Be hemodynamically stable and have systolic blood pressure (BP) above 100 mmHg and less than 160 mmHg and diastolic BP less than 95 mmHg at screening and baseline.
8. Have a body weight between 45 and 136 kg (99 and 300 lbs). For subjects weighing >113 kg (250 lbs), the vernakalant dose should be based on a weight of 113 kg (250 lbs) and not higher.

Exclusion Criteria

1. Known or suspected prolonged QT or uncorrected QT interval of >440 msec as measured at screening on a 12-lead ECG, familial long QT syndrome, or previous torsades de pointes, ventricular fibrillation; or sustained ventricular tachycardia (VT).
2. Symptomatic bradycardia, sick sinus syndrome, or ventricular rate less than 50 beats per minute (bpm) as documented by 12-lead ECG at screening.
3. A QRS interval >140 msec.
4. Any known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, pneumonia, acute pericarditis, myocarditis, or hypoxemia.
5. Atrial flutter.
6. Significant valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis.
7. Documented previous episodes of second or third degree atrioventricular (AV) block.
8. Had a myocardial infarction (MI), acute coronary syndrome or cardiac surgery within 30 days prior to entry into the study.
9. Uncorrected electrolyte imbalance of serum 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+ must be corrected prior to dosing.
10. Clinical evidence of digoxin toxicity in the opinion of the Investigator.
11. Failed electrical cardioversion during current episode of AF.
12. Received intravenous Class I or Class III antiarrhythmic drugs within 24 hours prior to dosing.
13. Received any oral Class I or Class III antiarrhythmic drugs for the purpose of conversion of AF to sinus rhythm within 24 hours prior to dosing.
14. Received amiodarone injection within 30 days prior to dosing, or oral amiodarone within 90 days prior to dosing.
15. A pacemaker.
16. Unstable congestive heart failure (CHF), Class IV CHF, or CHF requiring inotropes.
17. Serious pulmonary, hepatic, metabolic, renal, gastrointestinal, central nervous system or psychiatric disease, infection, febrile illness (oral temperature > 38.5°C), end stage disease states, or any other disease that could interfere with the conduct or validity of the study or compromise subject safety.
18. Have any evidence of an atrial thrombus.
19. Troponin (I or T) levels above the upper limit of normal.
20. Had a cerebrovascular accident within past 3 months.
21. Any other surgical or medical condition that, in the judgment of the clinical Investigator might warrant exclusion or be contraindicated for safety reasons.
22. Thyroid dysfunction, hypersensitivity to iodine, or any other condition for which amiodarone injection is contraindicated.
23. Had previous exposure to vernakalant.
24. Have known or suspected hypersensitivity to vernakalant injection or any component of its formulation, or amiodarone injection or any component of its formulation.
25. Be concurrently participating in another drug study or have received an investigational drug within 30 days prior to screening.
26. Be unable to communicate well with the Investigator and to comply with the requirements of the entire study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Efficacy assessments include assessment of conversion of AF to sinus rhythm at<br /><br>90 minutes after the start of treatment and assessment of symptom relief at 90<br /><br>minutes after the start of treatment. At 2 hours after the start of infusion,<br /><br>electrical cardioversion may be performed or rate control medication may be<br /><br>administered. Class I and Class III antiarrhythmics are not to be administered<br /><br>to the subject for 24 hours after the start of infusion. Subjects are to remain<br /><br>in the clinic for at least 6 hours after the start of infusion.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Subjects will attend a follow-up visit at 7 (±2) days after treatment and will<br /><br>receive a follow-up telephone call at 30 (±3) days for assessment of serious<br /><br>adverse events, concomitant medications related to serious adverse events, and<br /><br>recurrence of AF</p><br>

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