A Phase 1, Double-Blind, Randomized, Placebo-controlled, Single Ascending Dose Study of Flecainide Acetate Inhalation Solution to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers
- Conditions
- Recent Onset Paroxsymal Atrial FibrillationCardiovascular - Other cardiovascular diseases
- Registration Number
- ACTRN12616001156471
- Lead Sponsor
- InCarda Therapeutics Australia
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 44
To be eligible for randomization, the participants must meet the following criteria:
1.Be male (ages 18 to 35 years inclusive) or female (ages 18 to 50 years inclusive) at the time of screening;
2.Be female and of non-childbearing potential (e.g. post menopausal as demonstrated by FSH or surgical sterilization . i.e., tubal ligation or hysterectomy); males should wear condoms with female partners also using an acceptable form of contraception ;
3.Normal healthy volunteers with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol;
4.Have a BMI between 20 and 28 kg/m2, and a BW of 60-90 kg (for the dose range 20-70 mg) and 65-85 kg (for participants receiving 110 mg), inclusive;
5.No significant medical history, and in good general health;
6.Have no electrocardiographic abnormalities during a 12-Lead ECG screening and/or pre-dose assessment (measured after the participant is semi-recumbent for at least 5 minutes) that, in the opinion of the PI (or delegate), may compromise the participant’s safety in the study. Final study eligibility for the ECG criteria is to be approved by the PI and/or the SC;
7.Have no clinically significant abnormalities detected on a standard diagnostic echocardiogram;
8.Non-smokers (including tobacco, e-cigarettes and marijuana) – tested for the absence of cotinine in urine; Non-smokers with significant history of smoking, >5 pack years, are not eligible;
9.Be willing and able to comply with all study assessments and adhere to the protocol schedule;
10.Have suitable venous access for blood sampling;
11.Have ALT and AST within the normal range and Cockcroft-Gault estimated creatinine clearance >70 ml/min;
12.Have no abnormal finding of clinical relevance at the screening evaluation.
Participants with baseline pulmonary parameters that are borderline as the values listed in this table may be excluded at the discretion of the PI and/or SC.
ParameterBaseline enrollment criteria
*FEV1 (Forced Expiratory Volume in 1 second)FEV1 greater than or equal to 80% of normal values
*FVC (Forced Vital Capacity) FVC greater than or equal to 80% of normal values
FEF25-75% - report the value from the test with the highest sum of FEV1 + FVCgreater than 75% of predicted.
The average expired flow over the middle half of the FVC maneuver. It is regarded as a more sensitive measure of small airways narrowing than FEV1.
Chest X-rayNormal chest X-ray indicating no anomaly
Oxygen saturation monitor (performed before dosing and monitored every 15 mins up to 2hours than regularly until discharge)greater than 95%
*Report the largest value
http://www.nationalasthma.org.au/uploads/content/211-spirometer_handbook_naca.pdf
Inclusion and repeatability criteria for pulmonary function testing:
*Participants with less than 80% of predicted values will be excluded using Knudson 1976 similar to NIOSH - http://www.cdc.gov/niosh/topics/lung spirometry/refcalculator.html
*Obtain 3 acceptable tests, i.e. each test should meet the stated acceptability criteria. http://www.nationalasthma.org.au/uploads/content/211-spirometer_handbook_naca.pdf
*The two largest values for FVC should agree to within 0.15L
*The two largest values for FEV1 should agree to within 0.15L
Participants with ECG parameters that are borderline of the values listed in this table may be excluded at the discretion of the PI and/or the SC.
ParameterBaseline enrollment criteria
Heart Rate (HR)greater than or equal to 55 bpm (to 50bpm)
QRS intervalless than 100 ms (to 105 ms)
Systolic BPgreater than or equal to 100 to less than or equal to 160 mmHg
nclusion and repeatability criteria for pulmonary function testing:
*Participants with less than 80% of predicted values will be excluded using Knudson 1976 similar to NIOSH - http://www.cdc.gov/niosh/topics/lung spirometry/refcalculator.html
*Obtain 3 acceptable tests, i.e. each test should meet the stated acceptability criteria. http://www.nationalasthma.org.au/uploads/content/211-spirometer_handbook_naca.pdf
*The two largest values for FVC should agree to within 0.15L (this criteria has been removed)
*The two largest values for FEV1 should agree to within 0.15L (this criteria has been removed)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method