INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm (INSTANT)

Inclusion Criteria

• Subjects with recent-onset symptomatic AF at presentation,
• With a duration at onset of symptoms from 1 hour to 48 hours,
• And from one of the following categories:
• First detected episode of paroxysmal AF
• Recurrent episode of paroxysmal AF
• Episode post-cardiac ablation for paroxysmal AF

Subjects who:

• are prescribed a pill-in-the-pocket regimen (flecainide or propafenone) for paroxysmal AF, or
• are within 3 months of having undergone ablation of paroxysmal AF, or
• have experienced an episode of new AF but are not currently experiencing an episode of recent-onset paroxysmal AF, or
• are known to have paroxysmal AF (or previously diagnosed with paroxysmal AF) and have one or more previous symptomatic episodes but are not currently experiencing an episode of recent-onset paroxysmal AF may consent to pre-study screening prior to presenting with recent-onset symptomatic AF. These subjects will be eligible to receive study drug only when presenting with symptomatic paroxysmal AF of recent-onset (i.e., ≤ 48 hours), consenting to the full study, and after meeting all eligibility criteria.

Exclusion Criteria

• Subject 85 years of age
• Hemodynamic and/or cardiac instability, with systolic blood pressure 150 mmHg, and/or ventricular heart rate 150 bpm. For subjects to meet eligibility criteria, at least 2 of the 3 measurements of vital signs during screening (45, 30, and/or 15 minutes prior to dosing) must meet criteria.
• Current AF episode treated with Class I or Class III antiarrhythmic drugs or electrical cardioversion. Subjects whose current AF episode has been treated with flecainide are eligible if their total cumulative exposure to flecainide (including the study drug to be administered in this study) does not exceed 320 mg within a 24-hour period, per site standard of care.
• History of acute decompensated heart failure (HF)
• History within 6 months prior to screening of, or present HF with a left ventricular ejection fraction (LVEF) 2 mm] ST segment elevation or depression on ECG, echocardiographic findings suggestive of acute myocardial infarction), symptoms (e.g., angina pectoris, atypical angina pectoris), and/or being medicated with anti-anginal medication. In addition, subjects with signs of prior myocardial infarction (such as pathological Q waves) who are also taking concomitant medications for angina pectoris should be evaluated for presence of ongoing ischemia.
• History of myocardial infarction (MI) within 3 months of screening
• Known uncorrected severe aortic or mitral stenosis
• Hypertrophic cardiomyopathy with outflow tract obstruction
• Current diagnosis of persistent AF
• One or more episodes of atrial flutter within 6 months prior to screening or atrial flutter at presentation
• History of any of the following heart abnormalities:
• Long QT syndrome
• Conduction disease (e.g. second- or third- degree heart block, bundle brach block)
• Diagnosed with sinus node dysfunction (e.g., sick sinus syndrome) and/or one of the following:

(i) history of unexplained or cardiovascular syncope, (ii) known bradycardia suggestive of sinus node dysfunction, and/or (iii) prior electrical or pharmacological cardioversion associated with prolonged sinus or ventricular pause (e.g., >3 seconds) and/or slow ventricular rhythm (e.g., 75 years old. d) Brugada Syndrome e) Torsades de pointes (TdP)

• Any of the following ECG-related features:
• QTc interval >480 msec at screening (estimated by the Fridericia's formula)
• QRS duration ≥ 120 ms or history of previous documented wide QRS tachycardia
• Predominantly (i.e., >30%) paced heart rhythm
• Ventricular tachycardia (VT, sustained or non-sustained), or excessive premature ventricular complexes (PVCs, > 20 multifocal PVCs per hour), prior to dosing as per site telemetry. Site telemetry should be equipped with an alarm system for VT and PVCs or be continuously visually observed prior to dosing
• Severe renal imp