flecainide acetate oral inhalation solution (FlecIH-103) / InCarda - LARVOL DELTA

A Phase 1 Study of FlecIH-103 (Flecainide Acetate Inhalation Solution) Administered Using an Investigational, Single Use, Vibrating Mesh Nebulizer Delivery System to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers (ANZCTR) - P1 | N=48 | Completed | Sponsor: InCarda Therapeutics Australia, Pty. Ltd | Recruiting ➔ Completed

Trial completion • Atrial Fibrillation

Success stories from chemists in commercial roles: BMGT Nexus awardee (ACS-Fall 2025) - "Through real-world experiences, attendees will gain valuable perspectives on the skills, mindset shifts, and strategic decisions that enabled them to excel in their roles. This session provides inspiration and practical advice for scientists looking to leverage their expertise in a commercial role."

Flecainide acetate inhalation solution for cardioversion of recent-onset, symptomatic atrial fibrillation: results of the phase 3 RESTORE-1 trial. (PubMed, Europace) - "Despite early termination of the trial, FlecIH-103 was significantly more effective than placebo in cardioverting AF. Safety data did not show any serious AEs. Further studies of FlecIH-103 are needed to optimize the combination of drug formulation and inhalation delivery platform."

Journal • P3 data • Atrial Fibrillation • Cardiovascular • Cough • Pulmonary Disease • Respiratory Diseases

A Phase 1 Study of FlecIH-103 (Flecainide Acetate Inhalation Solution) Administered Using an Investigational, Single Use, Vibrating Mesh Nebulizer Delivery System to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers (ANZCTR) - P1 | N=48 | Recruiting | Sponsor: InCarda Therapeutics Australia, Pty. Ltd | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2024

Enrollment open • Trial initiation date • Atrial Fibrillation

Flecainide acetate inhalation solution for cardioversion of recent-onset, symptomatic atrial fibrillation: results of the phase 3 RESTORE-1 trial (ESC 2024) - "In an open-label, Phase 2 study (INSTANT), orally inhaled flecainide was safe and efficacious for acute conversion of PAF to sinus rhythm (SR).[1, 2] Purpose: Evaluate the efficacy and safety of flecainide acetate inhalation solution (FlecIH-103) compared to placebo in patients with short-duration, symptomatic, newly diagnosed, or recurrent PAF. Orally inhaled flecainide, at approximately half of the targeted dose, was modestly effective and safe. The 1.5-fold lower conversion rate observed in this study, compared to the same dose in the INSTANT trial, is consistent with the lower plasma levels of flecainide achieved. Future studies will be designed to improve drug delivery to yield peak plasma levels of flecainide associated with higher conversion rates."

P3 data • Atrial Fibrillation • Cardiovascular • Hypotension • Ventricular Tachycardia

Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial. (PubMed, JACC Clin Electrophysiol) - P2 | "The risk-benefit of orally inhaled FlecIH for acute cardioversion of recent-onset AF appears favorable. FlecIH could provide a safe, effective, and convenient first-line therapeutic option. (INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm [INSTANT]; NCT03539302)."

Journal • P2 data • Atrial Fibrillation • Cardiovascular • Cough • Pain • Respiratory Diseases

A Phase 1 Study of FlecIH-103 (Flecainide Acetate Inhalation Solution) Administered Using an Investigational, Single Use, Vibrating Mesh Nebulizer Delivery System to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers (ANZCTR) - P1 | N=44 | Not yet recruiting | Sponsor: InCarda Therapeutics Australia, Pty. Ltd

New P1 trial • Atrial Fibrillation

A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of FlecIH-104 in Healthy Volunteers (ANZCTR) - P1 | N=18 | Completed | Sponsor: InCarda Therapeutics Australia, Pty, Ltd | Recruiting ➔ Completed

Trial completion • Atrial Fibrillation • Cardiovascular

A Phase 1, Open-Label, Randomized, Single Dose Study of Flecainide Acetate Inhalation Solution (FlecIH-103) to Flecainide Acetate Intravenous Infusion (Tambocor®) to Compare Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers (ANZCTR) - P1 | N=18 | Completed | Sponsor: InCarda Therapeutics Australia Pty Ltd. | Not yet recruiting ➔ Completed

Trial completion • Atrial Fibrillation • Cardiovascular

Orally Inhaled Flecainide for the Conversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm: Final Results From the Phase 2 Instant Trial (AHA 2022) - "Introduction: The INSTANT trial was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset, symptomatic atrial fibrillation (AF) to sinus rhythm (SR)... The risk-benefit of orally inhaled flecainide acetate inhalation solution for acute cardioversion of recent onset AF appears favorable and may provide a safe, effective, and convenient first-line therapeutic option for AF conversion."

Clinical • P2 data • Atrial Fibrillation • Cardiovascular

INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm (INSTANT) (clinicaltrials.gov) - P2 | N=170 | Completed | Sponsor: InCarda Therapeutics, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Aug 2022 ➔ Jan 2022 | Trial primary completion date: Aug 2022 ➔ Jan 2022

Trial completion • Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

Predictors of successful cardioversion of recent-onset atrial fibrillation to sinus rhythm with orally inhaled flecainide (ESC 2022) - " Successful cardioversion of recent onset AF with 120 mg FlecIH was observed in normal, overweight, and obese patients with BMI values <35 kg/m2; however, conversion rate decreases with increasing BMI. Further evaluation of FlecIH dosing in severely obese patients is warranted."

Atrial Fibrillation • Cardiovascular

Alleviation of AF related symptoms following acute conversion of recent-onset, symptomatic atrial fibrillation to sinus rhythm with flecainide acetate oral inhalation solution (ESC 2022) - "The feasibility and safety of acute cardioversion of recent-onset (≤ 48 hours) symptomatic AF to SR with flecainide acetate oral inhalation (FlecIH) solution was shown in the Phase 2, open-label INSTANT trial. Conversion of recent onset AF to SR with inhaled flecainide was associated with a reduction in symptoms, normalization of heart rate, rapid hospital discharge and avoidance of ECV during a 5-day follow-up period."

Atrial Fibrillation • Cardiovascular

Open-Label, Multicenter Study of Flecainide Acetate Oral Inhalation Solution for Acute Conversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm. (PubMed, Circ Arrhythm Electrophysiol) - P2 | "Administration of flecainide via oral inhalation was shown to be safe and to yield plasma concentrations of flecainide sufficient to restore sinus rhythm in patients with recent-onset atrial fibrillation."

Clinical • Journal • Atrial Fibrillation • Cardiovascular • Cough • Pain • Respiratory Diseases

INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm (INSTANT) (clinicaltrials.gov) - P2; N=170; Active, not recruiting; Sponsor: InCarda Therapeutics, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Atrial Fibrillation • Cardiovascular

INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm (INSTANT) (clinicaltrials.gov) - P2; N=200; Recruiting; Sponsor: InCarda Therapeutics, Inc.; N=130 ➔ 200; Trial completion date: May 2021 ➔ Aug 2022; Trial primary completion date: May 2021 ➔ Aug 2022

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm (INSTANT) (clinicaltrials.gov) - P2; N=130; Recruiting; Sponsor: InCarda Therapeutics Australia Pty Ltd.; N=100 ➔ 130

Clinical • Enrollment change • Atrial Fibrillation • Cardiovascular

[VIRTUAL] An Open-label, Multicenter Study of Flecainide Acetate Oral Inhalation Solution Shows Acute Conversion of Recent-onset, Symptomatic Atrial Fibrillation to Sinus Rhythm in a Dose- and Concentration-dependent Manner (AHA 2020) - "FlecIH was well tolerated. Inhalation of FlecIH at the 120 mg dose yielded therapeutic plasma levels and conversion rates within the range reported for oral and IV administration."

Clinical • Atrial Fibrillation • Cardiovascular • Heart Failure • Pain • Respiratory Diseases

[VIRTUAL] Fast delivery of flecainide via the pulmonary (bolus) or intravenous (rapid infusion) routes reduces atrial fibrillation conversion dose and minimizes negative inotropic burden (ESC 2020) - "Rapid delivery of pulmonary or IV flecainide reduces the dose of drug required to achieve Cmax levels associated with conversion of AF. The attendant decrease across time in exposure of the ventricles to flecainide reduces QRS complex prolongation and the accompanying negative inotropic burden."

Atrial Fibrillation • Cardiovascular