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Trial registered on ANZCTR


Registration number
ACTRN12618001239257
Ethics application status
Approved
Date submitted
19/07/2018
Date registered
23/07/2018
Date last updated
9/07/2019
Date data sharing statement initially provided
9/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of FlecIH-101 Versus Placebo in Healthy Volunteers
Scientific title
A Phase 1, Double-Blind, Randomized, Placebo-controlled, Single Dose Study of FlecIH-101 (Flecainide Acetate Inhalation Solution) to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers
Secondary ID [1] 295605 0
FLE-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal atrial fibrillation 308925 0
Condition category
Condition code
Cardiovascular 307828 307828 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 301904 0
Treatment: Drugs
Comparator / control treatment
A single dose of sterile placebo inhalation solution (acetic acid and water for for injection, pH adjusted with sodium hydroxide) administered via oral inhalation in 3 inhalation stages, each lasting 3.5 minutes, with approximately 30-second breaks in between each inhalation.
Control group
Placebo

Outcomes
Primary outcome [1] 306807 0
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).
Timepoint [1] 306807 0
Adverse events will be recorded from the start of inhalation study drug on Day 1 through the end of the study (Day 9).
Secondary outcome [1] 349702 0
Pharmacokinetics (Cmax, Tmax, AUC0-24, AUCinf, 97kel, and T1/2) of the 90 mg dose of FlecIH-101 in plasma following administration of FlecIH-101 in healthy volunteers
Timepoint [1] 349702 0
Blood samples for pharmacokinetic analysis will be obtained at the following time points: pre-dose, during dosing (one sample during each of two approximately 30-second breaks in between each of the 3 inhalation stages and one sample at the end of dosing), and at 1, 3, 5, 10, 15, 30, and 60 minutes and 2, 4, 6, 12 and 24 hours after the completion of inhalation.
Secondary outcome [2] 349703 0
Pharmacodynamics of the 90 mg dose of FlecIH-101 by measuring electrocardiogram (ECG) intervals (QRS interval, PR interval, QTc, and JTc) following administration of FlecIH-101 in healthy volunteers
Timepoint [2] 349703 0
ECGs for pharmacodynamic analysis will be obtained at the following time points: prior to dosing (60, 45, 30, 25, and 15 minutes pre-dose), during dosing (one recording during each of two approximately 30-second breaks in between each of the 3 inhalation stages and one recording at the end of dosing), and at 1, 3, 5, 10, 15, 30, and 60 minutes and 2, 4, 12 and 24 hours after the completion of inhalation.

Eligibility
Key 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%
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involves contacting the holder of the allocation schedule who is the off-site pharmacist with no contact to participants
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using randomization envelopes
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Statistical Analysis will be performed using SAS v9.3 (SAS Institute, Cary, USA).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/09/2018
Actual
14/09/2018
Date of last participant enrolment
Anticipated
Actual
1/02/2019
Date of last data collection
Anticipated
Actual
6/03/2019
Sample size
Target
21
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11473 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 23494 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 300179 0
Commercial sector/Industry
Name [1] 300179 0
InCarda Therapeutics Australia, Pty, Ltd
Country [1] 300179 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
InCarda Therapeutics Australia, Pty, Ltd
Address
Level 13, 41 Exhibition Street
Melbourne
VIC 3000, Australia
Country
Australia
Secondary sponsor category [1] 299590 0
None
Name [1] 299590 0
Address [1] 299590 0
Country [1] 299590 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301011 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 301011 0
Ethics committee country [1] 301011 0
Australia
Date submitted for ethics approval [1] 301011 0
23/07/2018
Approval date [1] 301011 0
04/09/2018
Ethics approval number [1] 301011 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85594 0
Dr Ben Snyder
Address 85594 0
Nucleus Network
Level 5, Burnet Tower, AMREP Precinct,
89 Commercial Road,
Melbourne VIC 3004
Country 85594 0
Australia
Phone 85594 0
+61 (0)3 9076 8960
Fax 85594 0
Email 85594 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 85595 0
Stuart Gribble
Address 85595 0
Nucleus Network,
Level 5, Burnet Tower, AMREP Precinct,
89 Commercial Road,
Melbourne VIC 3004
Country 85595 0
Australia
Phone 85595 0
+61 (0)3 8535 4808
Fax 85595 0
Email 85595 0
s.gribble@nucleusnetwork.com.au
Contact person for scientific queries
Name 85596 0
David Fuller
Address 85596 0
INC Research/Inventiv Health,
Suite 1, Level 2, 924 Pacific Highway,
Gordon NSW 2027
Country 85596 0
Australia
Phone 85596 0
+61 (0)2 8437 9238
Fax 85596 0
Email 85596 0
david.fuller@syneoshealth.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.