Atrial Flutter, Symptomatic Atrial Fibrillation
Conditions
Keywords
vanoxerine, atrial fibrillation, atrial flutter, a-fib
Brief summary
Evaluate the safety and efficacy of a single oral dose of vanoxerine compared to placebo, in a dose modification manner, on the conversion of symptomatic atrial fibrillation (a-fib) or flutter of recent onset to normal sinus rhythm.
Detailed description
Vanoxerine has important antiarrhythmic properties and may prove effective in converting AF/AFL to sinus rhythm in subjects with a history of AF. This is a prospective, randomized, double-blinded, placebo-controlled, dose-modifying study in subjects who have been in symptomatic AF or AFL for more than 3 hours and less than 7 days as dated by symptoms, who have AF/AFL documented on ECG at the time of study drug administration, and who satisfy the inclusion and exclusion criteria. The primary objectives of the trial are to evaluate the safety and efficacy of a single oral dose of vanoxerine compared to placebo following oral administration.
Interventions
DRUGVanoxerine
single oral dose
DRUGPlacebo
single oral dose
Sponsors
Laguna Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* provide written informed consent, * male or female 18 years of age or greater; women of child bearing potential must use adequate contraception * symptomatic AF/AFL for more than 3 hours and less than 7 days (168 hours), as dated by symptoms * AF/AFL documented by ECG at the start of study drug administration
Exclusion criteria
* Systolic blood pressure \<100 mmHg. * Average heart rate \<50 bpm. * Average QTcF (Fridericia correction) \>440 ms. * Average QRS interval \>140 ms. * Paced atrial or ventricular rhythm on ECG. * Serum potassium \<3.5 meq/L (may be corrected prior to randomization). * Received another intravenous Class I or Class III antiarrhythmic drug within prior 3 days. * received amiodarone (oral or IV) in prior 3 months. * Clinical evidence or history of acute coronary syndrome within 30 days prior to randomization. * Aortic stenosis with aortic valve area equal to or less than 1.0 cm2. * Rheumatic mitral stenosis with valve area of \<1.5 cm2. * Untreated hyperthyroidism. * Acute pericarditis. * AF/AFL as a result of surgery within the last 7 days * History of failed electrical cardioversion * History of polymorphic ventricular tachycardia (PVT, e.g. torsades de pointes). * History or family history of long QT syndrome. * History of ventricular tachycardia requiring drug or device therapy. * History of NYHA Heart Failure Class 3 or 4 or recent (within 1 month) onset of heart failure not related to rapid ventricular response AF. * Ejection fraction (EF) of 35% or less.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Conversion to Sinus Rhythm | baseline through 4 hours | proportion of subjects who convert to sinus rhythm through 4 hours after start of study drug |
Countries
Israel, Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo to match vanoxerine oral capsule
Placebo: single oral dose | 32 |
| Vanoxerine 200mg vanoxerine oral capsule, 200mg
Vanoxerine: single oral dose | 22 |
| Vanoxerine 300mg vanoxerine oral capsule, 300mg
Vanoxerine: single oral dose | 25 |
| Vanoxerine 400mg vanoxerine oral capsule, 400mg
Vanoxerine: single oral dose | 25 |
| Total | 104 |
Baseline characteristics
| Characteristic | Vanoxerine 400mg | Total | Placebo | Vanoxerine 200mg | Vanoxerine 300mg |
|---|---|---|---|---|---|
| Age, Continuous | 68.4 years STANDARD_DEVIATION 9.6 | 64 years STANDARD_DEVIATION 11 | 62.3 years STANDARD_DEVIATION 12.2 | 61.7 years STANDARD_DEVIATION 12.2 | 63.4 years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 13 Participants | 41 Participants | 10 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Male | 12 Participants | 63 Participants | 22 Participants | 13 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 32 | 3 / 22 | 8 / 25 | 17 / 25 |
| serious Total, serious adverse events | 0 / 32 | 1 / 22 | 1 / 25 | 0 / 25 |
Outcome results
Primary
Conversion to Sinus Rhythm
proportion of subjects who convert to sinus rhythm through 4 hours after start of study drug
Time frame: baseline through 4 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Conversion to Sinus Rhythm | 4 participants |
| Vanoxerine 200mg | Conversion to Sinus Rhythm | 4 participants |
| Vanoxerine 300mg | Conversion to Sinus Rhythm | 11 participants |
| Vanoxerine 400mg | Conversion to Sinus Rhythm | 13 participants |
Primary
Conversion to Sinus Rhythm
proportion of subjects who convert to sinus rhythm through 24 hours after start of study drug
Time frame: baseline through 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Conversion to Sinus Rhythm | 10 participants |
| Vanoxerine 200mg | Conversion to Sinus Rhythm | 13 participants |
| Vanoxerine 300mg | Conversion to Sinus Rhythm | 16 participants |
| Vanoxerine 400mg | Conversion to Sinus Rhythm | 21 participants |