A Phase 1, Open-Label, Randomized, Single Dose Study of Flecainide Acetate Inhalation Solution (FlecIH-103) to Flecainide Acetate Intravenous Infusion (Tambocor®) to Compare Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers

Exclusion Criteria24

• Evidence of asthma, chronic obstructive pulmonary disease (COPD) or major pulmonary airway disease, including participants with established pulmonary disease in need of inhalation medication; (participants with history of childhood asthma but no subsequent episodes are eligible)
• Evidence of early repolarization pattern in the ECG, defined as elevated J-Point or end-QRS slurring with or without concave ST-segment elevation [MacFarlane, 2015]. A J-Point elevation of greater than or equal to 0.1 mV and prominent end-QRS notch or slur in 2 contiguous ECG leads should be flagged for review by the study cardiologist and/or medical monitor. Minor findings are considered acceptable.
• History of heart disease such as, coronary artery disease, MI, cardiac arrhythmias, valvular heart disease and heart failure.
• Previous invasive cardiac procedures (participants having undergone invasive cardiac procedures which definitively demonstrated no cardiac issues are eligible);
• Clinically significant family history of cardiac arrhythmias, acquired or congenital (e.g., Brugada and/or long-QT syndromes), unexplained sudden cardiac death, and/or unexplained syncope
• Family history of congenital airway lung obstructive disease
• Use of prescription medication or over-the-counter products (including other antiarrhythmic drugs, anticoagulants and BP lowering drugs, medications known to prolong the QTc interval, natural food supplements, vitamins, and garlic as a supplement) within 7 days prior to administration of study treatment, except for topical products without systemic absorption, paracetamol, and/or protocol-compliant contraceptives
• Any contraindications to flecainide as per Tambocor package insert
• Has experienced any symptomatic heart failure (per New York Heart Association [NYHA] guidelines), or history of impaired LVEF.
• Has human immunodeficiency virus infection, as shown by the presence of anti-human immunodeficiency virus (HIV) antibody (sero-positive).
• Is sero-positive for hepatitis B or hepatitis C virus, and/or a history of delta virus hepatitis.
• Has uncontrolled hypertension: Blood pressure (BP) greater than 150/100 mmHg.
• Has a history of torsades de pointes, atrial and/or ventricular rhythm disturbances (e.g., atrial or ventricular tachycardia or fibrillation), sinus bradycardia (less than or equal to 47 bpm), Cardiac Conduction Disease (AV Nodal Block or PR interval greater than 190 ms), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG.
• Has had episodes of syncope, including during blood draw.
• Currently abuses and/or has a history of alcohol and/or drug abuse less than 12 months from Screening.
• Regularly uses excessive alcohol within six months prior to the Screening visit (i.e., more than fourteen units of alcohol per week [1 Unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40 % alcohol]).
• Has a positive standard 10x panel drug test at Screening and/or has a history of drug abuse within 12 months from Screening.
• Use of investigational agents or devices within 30 days or 5 half-lives (whichever is longer) prior to planned study dosing or current participation in an investigational study
• Has a clinically significant history or presence of any gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Has any clinically significant history or presence of neurological, endocrine, cardiovascular, pulmonary, haematological, immunologic, psychiatric, metabolic or other uncontrolled systemic disease.
• Has donated blood (greater than or equal to 500 mL) within 7 days prior to study treatment administration. Donation or loss of whole blood (excluding the volume of blood that will be drawn during the screening procedures of this study) prior to administration of the study treatment as follows: 50 mL to 499 mL of whole blood within 30 days, or more than 499 mL of whole blood within 56 days prior to study treatment administration.
• Presence of any concomitant medical or psychiatric condition or social situation that, in the opinion of the PI, would make it difficult to comply with protocol requirements or put the participant at additional safety risk
• Is unable or unwilling to return for all scheduled study visits.
• Has any other condition that, in the opinion, of the PI would render the participant unsuitable for enrolment or could interfere with his/her participation in the study.