Flecainide Acetate Inhalation Solution for Cardioversion of Recent-Onset, Symptomatic Atrial Fibrillation

NCT05039359 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: FLE-007
• Study Type: interventional
• Target: 54
• Locations: 6 countries
• Sites: 40

Brief Summary

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical study designed to evaluate the efficacy and safety of FlecIH-103 (flecainide acetate inhalation solution) compared with placebo in patients with recent-onset, symptomatic newly diagnosed or paroxysmal AF. Approximately 400 patients are expected to be enrolled in this study. Patients will be randomized 3:1 to receive FlecIH-103 at a total dose of up to 120 mg estimated total lung dose (eTLD) (n=300) or placebo inhalation solution (n=100). Randomization will be stratified by geographic region (US and ex-US) and duration of symptoms of the current AF episode (≥1 hour to ≤24 hours and \>24 hours to ≤48 hours).

Conditions

Paroxysmal Atrial Fibrillation

Keywords

atrial fibrillation

Outcome Measures

Primary Outcomes (1)

• Assessment of proportion of patients whose AF converts using continuous ECG monitoring

  To compare the efficacy of flecainide acetate inhalation solution and placebo for the conversion of atrial fibrillation (AF) to sinus rhythm (SR) in patients with recent-onset, symptomatic newly diagnosed or paroxysmal AF. Conversion from AF to SR will be monitored via continuous ECG recording. The efficacy of flecainide acetate solution and placebo will be compared using conversion as recorded on the ECG.

  90 minutes

Secondary Outcomes (5)

• Time of conversion to be monitored using continuous ECGs

  90 minutes

• Assessing and comparing the AF related symptoms by using a questionnaire

  90 minutes post dose

• Assessing and comparing the hospital admissions between the active vs. placebo

  90 minutes

• Assessing and comparing the AF-related interventions prior to discharge between the active vs. placebo

  90 minutes

• Assessing and comparing the time of discharge

  90 minutes

Study Arms (2)

FlecIH-103 (flecainide acetate inhalation solution)

ACTIVE COMPARATOR

Up to two 3.5-minute inhalations separated by a 1-minute break, for a total duration of up to 8 minutes on Day 1. Dosing will continue until conversion of AF to SR is observed for ≥1 minute or the full dose (120 mg eTLD) is administered, whichever occurs first.

Drug: FlecIH-103

Vehicle-matched inhalation solution (placebo)

PLACEBO COMPARATOR

Up to two 3.5-minute inhalations separated by a 1-minute break, for a total duration of up to 8 minutes on Day 1.

Drug: FlecIH-103

Interventions

FlecIH-103 DRUG

flecainide acetate inhalation solution

FlecIH-103 (flecainide acetate inhalation solution); Vehicle-matched inhalation solution (placebo)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 and ≤85 years of age
• Recent onset of symptomatic newly diagnosed or paroxysmal AF
• Recent onset is defined as a symptom duration ≥1 and ≤48 hours at time of dosing
• Newly diagnosed AF is AF that has not been diagnosed previously, independent of its duration
• Paroxysmal AF is defined as recurrent AF in a patient whose previous AF episode(s) self-terminated (ie, without treatment) or terminated with intervention ≤7 days of onset.
• A symptomatic recent-onset AF episode post cardiac ablation for paroxysmal AF would be considered eligible

You may not qualify if:

• History of non self-terminating AF/AFL as defined by
• One or more failed attempts to restore SR with pharmacological therapy
• ECV procedure for an AF episode ≤1 year prior to screening. Exception: One (1) prior ECV is allowed if no option for pharmacological conversion was previously available
• More than 3 ECV procedures in ≤5 years prior to screening
• Current diagnosis of persistent AF
• Persistent AF defined as AF that is continuously sustained \>7 days, including episodes terminated by cardioversion (drugs or electrical cardioversion) after \>7 days. Patients with persistent AF do not have self-terminating AF episodes
• Patients who have undergone an ablation procedure for persistent AF are not eligible
• One or more episodes of AFL ≤6 months prior to randomization
• a. Exception: a patient who has received ablation for AFL ≤3 months prior to screening with no recurrence of AFL prior to randomization is considered eligible Vital signs
• Hemodynamic or cardiac instability during AF, defined as any of the following:
• Systolic blood pressure \<100 or ≥160 mmHg
• Diastolic blood pressure ≥95 mmHg
• Ventricular heart rate \<80 or \>160 bpm
• Respiratory rate \>22 breaths per minute Relevant structural heart disease
• History of decompensated heart failure (HF)

Sponsors & Collaborators

• InCarda Therapeutics, Inc.: lead

Study Sites (40)

UC Davis Medical Center

Davis, California, 95819, United States

Location

Memorial Care

Long Beach, California, 90806, United States

Location

Bridgeport Hospital

Bridgeport, Connecticut, 06610, United States

Location

Orlando Health Heart and Vascular Institute and Orlando Regional medical Center

Orlando, Florida, 32806, United States

Location

Tampa General Hospital; Center of Research Excellence

Tampa, Florida, 33606, United States

Location

IU Health Ball Memorial Hospital

Muncie, Indiana, 47303, United States

Location

Reid Physician Associates

Richmond, Indiana, 47374, United States

Location

North Kansas City Hospital

Kansas City, Kansas, 64116, United States

Location

University of Kansas Medical Center Research Institute

Kansas City, Kansas, 66160, United States

Location

Saint Michaels Medical Center

Newark, New Jersey, 07102, United States

Location

The Valley Hospital, Inc

Ridgewood, New Jersey, 07450, United States

Location

Mount Sinal Hospital

New York, New York, 10019, United States

Location

Weill Cornell Medical Center

New York, New York, 10021, United States

Location

University of Cincinnati College of Medicine

Cincinnati, Ohio, 45267, United States

Location

The MetroHealth System

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic Emergency Department

Cleveland, Ohio, 44195, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Reading Hospital

Reading, Pennsylvania, 19611, United States

Location

EDUMED s.r.o.

Náchod, 54701, Czechia

Location

Nemocnice Slany

Slaný, 27401, Czechia

Location

DPC Hospital Egyesitett Szent Istvan es Szent Laszlo Korhaz

Budapest, 1097, Hungary

Location

University of PACs

Pécs, 7624, Hungary

Location

Deventer Ziekenhuis

Deventer, 7417 SE, Netherlands

Location

Ziekenhuis Gelderse Vallei

Ede, 6716RP, Netherlands

Location

Admiraal de Ruyter Ziekenhuis

Goes, 4462 RA, Netherlands

Location

Universitair Medisch Centrum Groningen (UMCG)

Groningen, 9713 GZ, Netherlands

Location

Spaarne Gasthuis

Haarlem, 2035 RC, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, 8934 AD, Netherlands

Location

Diakonessenhuis

Utrecht, 3582 KE, Netherlands

Location

Maxima Medisch Centrum

Veldhoven, 5504 DB, Netherlands

Location

Mazowiecki Szpital Specjalistyczny w Ostrolece

Ostrołęka, 07-410, Poland

Location

Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu

Torun, 87-100, Poland

Location

Hospital General Universitario de Alicante

Alicante, 3010, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

La Paz Univerisity Hospital

Madrid, 28046, Spain

Location

Hospital Universitario Puera de Hierro

Madrid, 28222, Spain

Location

Fundacion Hospital Son Liatzer

Palma de Mallorca, 7198, Spain

Location

Hospital Santiago De Compostela

Santiago de Compostela, 15706, Spain

Location

Related Publications (1)

• Rienstra M, Woite-Silva AC, Kuijper A, Eijsbouts S, Kraaier K, Janota T, Van Ofwegen C, Tuininga Y, Badings E, Merino JL, Ruskin JN, Camm AJ, Kowey PR, Dufton C, Maupas J, Parsell D, Belardinelli L. Flecainide acetate inhalation solution for cardioversion of recent-onset, symptomatic atrial fibrillation: results of the phase 3 RESTORE-1 trial. Europace. 2025 Mar 28;27(4):euaf064. doi: 10.1093/europace/euaf064.

  PMID: 40132102 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Luiz Belardinelli, MD

  InCarda Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo controlled

Study Record Dates

• First Submitted: August 9, 2021
• First Posted: September 9, 2021
• Study Start: April 26, 2022
• Primary Completion: May 22, 2023
• Study Completion: May 22, 2023
• Last Updated: October 30, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (2); NL (8); HU (2); PL (2); US (18); ES (8)