INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm (INSTANT)

Subjects eligible to participate in the study must provide written informed consent (IC) before randomization or any study- specific procedures.

The study consists of 3 parts (Part A, Part B and Part C) as described below:

Part A: was completed in March 2020 and was an open-label, randomized, multicenter design to evaluate the feasibility of administration of inhaled flecainide in two dosing regimens.

Subjects were randomized at a 1:1 ratio to a single (N = 10) or repeat (N = 10) dose regimen. Randomization, for the initial 20 patients in Part A was stratified by duration of the presenting AF episode (≥ 1 h up to ≤ 24 hours; \> 24h up to ≤ 48h).

After completion of the 60 mg dose cohort and review of safety/tolerability and PK data, additional subjects were enrolled in an additional repeat dose regimen (90 mg estimated total lung dose (TLD), N= up to 30 subjects. An additional dose cohort of 120 mg was added to Part A which utilized a different concentration of flecainide (75 mg/mL) and formulation (FlecIH-103). The final dose of 120 mg was selected as the dose to continue evaluating in Part B.

Part B: was an open-label, multicenter design to confirm the safety (including tolerability) and efficacy of the optimal inhaled flecainide dose determined from Part A (120 mg, using the FlecIH-103 inhalation solution).

Part C: was an open-label, multi center design study with exploratory objectives to explore the feasibility of patient-led self administration of flecainide. Part C also included an exploratory sub-study to assess the feasibility of implementing a portable cardiac ultrasound (HHE) at screening in an emergent setting.

Upon return to the clinic with a recurrent episode of AF, eligibility was reconfirmed and the subjects self-administered the study treatment and inhalation regimen under medical supervision.

If at 90 minutes after initiation of dosing, no conversion to sinus rhythm (SR) was observed, the Investigator was allowed to offer the subject another appropriate therapy. Discharge was left up to the discretion of the treating physician but no less than 90 min after initiation of dosing. Heart rhythm was confirmed with an Event Recorder during follow up.

An independent Data and Safety Monitoring Board (DSMB) was responsible for monitoring safety during the study.