A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of FlecIH-101 Versus Placebo in Healthy Volunteers

Phase 1

Completed

• Conditions: Paroxysmal atrial fibrillation; Cardiovascular - Other cardiovascular diseases

• Registration Number: ACTRN12618001239257
• Lead Sponsor: InCarda Therapeutics Australia, Pty, Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-07-23
• Study Completion: 2019-03-06
• Last Update Posted: 22 July 2019

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 22

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 p

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate the safety and tolerability of a single 90mg dose of FlecIH-101 compared to placebo in healthy volunteers. This will be assessed by looking at the incidence, severity, causality and seriousness of adverse events; changes in clinical laboratory evaluations; changes in vital signs parameters, physical examinations; and ECGs (electrocardiograms).[Adverse events will be recorded from the start of inhalation study drug on Day 1 through the end of the study (Day 9).]