Flecainide Acetate Inhalation Solution for Cardioversion of Recent-Onset, Symptomatic Atrial Fibrillation

Exclusion Criteria

• •1. History of non self-terminating AF/AFL as defined by
• •1. One or more failed attempts to restore SR with pharmacological therapy
• •2. ECV procedure for an AF episode ≤1 year prior to screening. Exception: One (1) prior ECV is allowed if no option for pharmacological conversion was previously available
• •3. More than 3 ECV procedures in ≤5 years prior to screening
• •2. Current diagnosis of persistent AF
• •1. Persistent AF defined as AF that is continuously sustained \>7 days, including episodes terminated by cardioversion (drugs or electrical cardioversion) after \>7 days. Patients with persistent AF do not have self-terminating AF episodes
• •3. One or more episodes of AFL ≤6 months prior to randomization
• •a. Exception: a patient who has received ablation for AFL ≤3 months prior to screening with no recurrence of AFL prior to randomization is considered eligible Vital signs
• •4. Hemodynamic or cardiac instability during AF, defined as any of the following:
• •1. Systolic blood pressure \<100 or ≥160 mmHg
• •2. Diastolic blood pressure ≥95 mmHg
• •3. Ventricular heart rate \<80 or \>160 bpm
• •5. Respiratory rate \>22 breaths per minute Relevant structural heart disease
• •6. History of decompensated heart failure (HF)
• •7. Evidence of significant HF defined as any of the following:
• •a. Hospitalization in the last 12 months for HF or suspected HF event b. Most recent assessment of left ventricular ejection fraction (LVEF) \<45% i. For patients in the United States, a standard diagnostic echocardiogram assessed ≤180 days prior to screening is required to ascertain eligibility. If none is available, the patient must undergo a standard diagnostic echocardiogram or a diagnostic echocardiogram using a portable ultrasound device (handheld echocardiogram \[HHE\]) during screening to confirm eligibility c. New York Heart Association (NYHA) Class II-IV symptoms d. Medication history suggestive of HF per the Investigator's discretion
• •8. Signs or symptoms of ongoing myocardial ischemia, including any of the following:
• •1. Significant ST segment elevation or depression (ie, ≥2 mm) on a standard 12-lead ECG
• •2. Echocardiogram findings (eg, wall motion abnormalities) suggestive of acute myocardial infarction (MI)
• •3. Angina pectoris, atypical angina pectoris, or receiving antianginal medication for ischemia
• •9. History of MI ≤3 months of screening
• •10. History of uncorrected moderate or severe aortic or mitral valvular stenosis, in the opinion of the Investigator
• •a. If an echocardiogram is performed at screening, moderate or severe valve disease observed during the examination is considered exclusionary
• •11. History of LV hypertrophy with LV thickness \>12 mm as observed in the most recent assessment, ie, an echocardiogram Other CV conditions
• •12. Stroke (including transient ischemic attack) ≤3 months prior to randomization
• •13. History of any of the following cardiac abnormalities:
• •1. Long QT syndrome
• •2. Conduction system disease (eg, PR interval \>200 ms, second- or third degree heart block, bundle branch block)
• •3. Brugada syndrome
• •4. Torsade de pointes
• •5. Diagnosed with sinus node dysfunction (eg, sick sinus syndrome) or any of the following:
• •i. History of unexplained or cardiovascular syncope ii. Bradycardia suggestive of sinus node dysfunction iii. Prior electrical or pharmacological cardioversion associated with sinus or ventricular pause \>3 seconds or ventricular heart rate \<45 bpm at time of conversion
• •14. Any of the following ECG-related features at screening:
• •1. QT interval corrected for heart rate using the Fridericia formula (QTcF) \>480 msec
• •2. Wide QRS complex (ie, duration ≥120 msec) or history of documented wide QRS complex tachycardia (ie, wide QRS complex with ventricular heart rate \>100 bpm)
• •3. Presence of ventricular tachycardia (VT). Site telemetry should be equipped with an alarm system for VT and PVCs or be continuously visually observed prior to dosing
• •15. Presence of a pacemaker
• •16. Cardiac surgery for any of the exclusionary conditions (eg, valvular disease, hypertrophy, coronary artery disease) ≤6 months prior to randomization Prior and concomitant non-CV conditions
• •17. Known severe renal impairment or patient receiving dialysis
• •18. Known abnormal liver function, including hepatic disease or biochemical evidence of significant liver derangement
• •19. Uncorrected hypokalemia
• •1. Hypokalemia is defined as serum potassium below the normal range according to the local laboratory reference ranges at screening
• •2. If serum potassium is below the normal range at screening, therapeutic correction (eg, potassium supplementation) is required
• •20. Uncorrected hypomagnesemia
• •1. Hypomagnesemia is defined as serum magnesium below the normal range according to the local laboratory reference ranges at screening
• •2. If serum magnesium result is below the normal range at screening, therapeutic correction (eg, magnesium supplementation) is required
• •21. Chronic obstructive pulmonary disease or other established pulmonary disease in need of inhalation medication
• •a. Exception: patients with intermittent mild asthma who are not experiencing active symptoms at screening, and whose asthma is well controlled with as-needed administration of a bronchodilator ≤2 days/week, and who has not experienced ≥2 exacerbations requiring oral systemic corticosteroids ≤1 year prior to screening
• •22. History of bronchospasm (eg, hyperreactive airways to inhalants) or difficulty inhaling medications
• •23. Previous or current hospitalization for COVID-19, or any secondary cardiomyopathy from COVID-19 Prior and concomitant medications and procedures
• •24. Treatment with Class I or III AADs ≤7 days prior to randomization
• •25. Treatment with amiodarone ≤12 weeks prior to randomization
• •26. Known hypersensitivity to flecainide acetate, any active metabolites of flecainide acetate, or any excipients in FlecIH-103
• •27. Any condition or circumstance which in the opinion of the Investigator may make the patient unsuitable for the study, such as:
• •1. High risk for stroke based on the screening coagulation panel or medical history per Investigator's discretion (eg, CHA2DS2-VASc score)
• •2. Congenital heart disease
• •3. AF that is secondary to electrolyte imbalance, thyroid disease, or other reversible or non-cardiovascular cause
• •4. A serious or life-threatening medical condition
• •5. An acute infection
• •28. Known drug or alcohol dependence ≤12 months prior to screening as judged by the Investigator
• •29. A body mass index ≥35 kg/m2
• •30. Legally incompetent to provide informed consent
• •31. Previous treatment with any other investigational drug ≤30 days from screening or 5 half-lives of the drug, whichever is longer
• •32. Female of childbearing potential defined as any of the following:
• •1. Not surgically sterile or postmenopausal (Appendix 1)
• •2. A negative pregnancy test is unavailable at screening
• •3. Pregnant or breastfeeding at screening
• •33. Males whose sexual partners are women of childbearing potential (WOCBP) must use at least one highly effective method of contraception during the study unless permenantly sterile by bilateral orchiectomy.