None listed
Conditions
Brief summary
This research project is being conducted to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of a single 90 mg dose of FlecIH-101 when administered in healthy adult subjects via oral inhalation.
Interventions
A single 90 mg dose of FlecIH-101 (flecainide acetate inhalation solution) administered via oral inhalation in 3 inhalation stages, each lasting 3.5 minutes, with approximately 30-second breaks in between each inhalation. Monitoring of adherence to the inhalation procedure will be done by direct observation by study personnel. If participants provide specific written consent, a video recording will also be taken of the inhalation procedure.
Sponsors
InCarda Therapeutics Australia, Pty, Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female, 18 to 55 years of age (inclusive), at the time of screening; 2. Agree to use protocol specified method(s) of contraception, if a male participant or a female participant of childbearing potential who engages in heterosexual intercourse; 3. Agree to refrain from egg or sperm donation for the duration of the study; 4. Able and willing to sign the informed consent as approved by the Human Research Ethics Committee (HREC); 5. Have a body mass index (BMI) between 20 and 32 kg/m2 and a BW greater than or equal to 55 kg; 6. No significant medical history, and in good general health; 7. Have no electrocardiographic abnormalities during a 12-lead ECG screening that, in the opinion of the PI (or delegate), may compromise the participant’s safety in the study; 8. Have no clinically significant abnormalities detected on a standard diagnostic echocardiogram; 9. Be non-smokers (including tobacco, e-cigarettes and marijuana) without a significant smoking history (former cigarette smokers with less than or equal to 5 pack years history are eligible). Participants will be tested for the absence of cotinine in urine; 10. Be willing and able to comply with all study assessments and adhere to the protocol schedule; 11. Have suitable venous access for blood sampling and/or injection of medication if needed; 12. Have alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values < 1.5 times the upper limit of normal (ULN) and Cockcroft-Gault estimated creatinine clearance > 70 mL/min at screening; 13. Have electrolytes within the normal range (specifically potassium greater than or equal to 3.8 MEq/L) at screening; 14. Have no abnormal finding of clinical significance at screening; 15. Has specific cardiovascular parameters measured using a 12 lead ECG and other hemodynamic criteria: Heart Rate (HR): greater than or equal to 50 bpm PR Interval: less than or equal to 190 ms QRS interval: less than or equal to 105 ms QTcF duration: less than or equal to 450 ms for males, less than or equal to 460 ms for females Systolic BP: between 90 and 140 mmHg, inclusive Diastolic BP: between 60 and 100 mmHg3, inclusive 16. Has specific pulmonary parameters related to pulmonary function: FEV1 (forced expiratory volume in 1 second): greater than or equal to 80% of normal values FVC (forced vital capacity): greater than or equal to 80% of normal values FEF (forced expiratory flow) 25-75%: greater than 75% of predicted. Chest X-ray: Normal chest X-ray indicating no clinically significant anomaly Oxygen saturation: greater than 95%
Exclusion criteria
1. 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); 2. Evidence of early repolarization pattern in the ECG, defined as elevated J-Point or end-QRS slurring with or without concave ST-segment elevation; 3. History of heart disease such as, coronary artery disease, MI, cardiac arrhythmias, valvular heart disease and heart failure; 4. Previous invasive cardiac procedures (participants having undergone invasive cardiac procedures which definitively demonstrated no cardiac issues are eligible); 5. 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; 6. Family history of congenital airway lung obstructive disease; 7. Use of prescription medication or over-the-counter products (including other antiarrhythmic drugs, anticoagulants and blood pressure 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 oral contraceptives; 8. Any contraindications to flecainide as per Tambocor™ package insert; 9. Has experienced any symptomatic heart failure (per New York Heart Association [NYHA] guidelines), or history of impaired LVEF; 10. Has human immunodeficiency virus infection, as shown by the presence of anti human immunodeficiency virus (HIV) antibody (sero-positive); 11. Is sero-positive for hepatitis B or hepatitis C virus, and/or a history of delta virus hepatitis; 12. Has uncontrolled hypertension: blood pressure (BP) greater than 150/100 mmHg; 13. 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 50 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; 14. Has had episodes of syncope, including during blood draw; 15. Currently abuses and/or has a history of alcohol and/or drug abuse less than 12 months from screening; 16. Regularly uses excessive alcohol within six months prior to the screening visit (i.e., more than fourteen units of alcohol per week [1 Unit equals 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]); 17. Use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, heroin, phencyclidine [PCP] and crack) within 1 year prior to the screening visit or positive urine drug screen at screening; 18. 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; 19. 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; 20. Has any clinically significant history or presence of neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, metabolic or other uncontrolled systemic disease; 21. 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; 22. 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; 23. Is unable or unwilling to return for all scheduled study visits; 24. Has any other condition that, in the opinion, of the PI would render the participant unsuitable for enrollment or could interfere with his/her participation in the study.
Outcome results
None listed