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

NCT03539302 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: FLE-002
• Study Type: interventional
• Target: 176
• Locations: 2 countries
• Sites: 9

Brief Summary

The study consisted of 3 parts (Part A, Part B and Part C). Part A was an open-label, randomized, multi center design to evaluate the feasibility of administration of inhaled flecainide in two dosing regimens. 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. Part C was an open-label, multi center 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.

Conditions

Paroxysmal Atrial Fibrillation (PAF)

Keywords

Inhaled Flecainide

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Successful Conversion of Atrial Fibrillation to Sinus Rhythm

  To evaluate the conversion of AF to SR and symptom relief by inhaled flecainide acetate inhalation solution, under two oral inhalation dosing regimens in subjects with recent onset of paroxysmal AF. The subjects will be monitored via ECG and telemetry while in the hospital for 90 minutes.

  90 minutes

Secondary Outcomes (2)

• PK Objectives by Analyzing Blood Samples to Evaluate Peak Plasma Concentration (Cmax)

  90 minutes

• Pharmacodynamics (PD) Objectives by Performing Serial 12-Lead ECG Recordings (Changes in QRS)

  90 minutes

Study Arms (1)

Repeat dose inhaled flecainide acetate

EXPERIMENTAL

One 120 mg dose of flecainide acetate inhalation solution will be administered via two oral inhalations of 3.5 minutes. There will be a 1 minute break between the two inhalations. A single nebulizer will be used. A subset of enrolled patients will be included in a sub-study in which a Hand Held ECHO device at bedside will be used to confirm eligibility by verifying absence of structural heart disease. Once eligibility is confirmed the treatment for this subset of patients will be the same as described above; one 120 mg dose of flecainide acetate inhalation solution will be administered via two oral inhalations of 3.5 minutes. There will be a 1 minute break between the two inhalations. A single nebulizer will be used.

Drug: Flecainide Acetate

Interventions

Flecainide Acetate DRUG

Oral inhalation form using a nebulizer

Also known as: FlecIH

Repeat dose inhaled flecainide acetate

Eligibility Criteria

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

You may qualify if:

• Subjects with recent-onset symptomatic AF at presentation,
• With a duration at onset of symptoms from 1 hour to 48 hours,
• And from one of the following categories:
• First detected episode of paroxysmal AF
• Recurrent episode of paroxysmal AF
• Episode post-cardiac ablation for paroxysmal AF
• Subjects who:
• are prescribed a pill-in-the-pocket regimen (flecainide or propafenone) for paroxysmal AF, or
• are within 3 months of having undergone ablation of paroxysmal AF, or
• have experienced an episode of new AF but are not currently experiencing an episode of recent-onset paroxysmal AF, or
• are known to have paroxysmal AF (or previously diagnosed with paroxysmal AF) and have one or more previous symptomatic episodes but are not currently experiencing an episode of recent-onset paroxysmal AF may consent to pre-study screening prior to presenting with recent-onset symptomatic AF. These subjects will be eligible to receive study drug only when presenting with symptomatic paroxysmal AF of recent-onset (i.e., ≤ 48 hours), consenting to the full study, and after meeting all eligibility criteria.

You may not qualify if:

• Subject \< 18 or \> 85 years of age
• Hemodynamic and/or cardiac instability, with systolic blood pressure \< 100 mmHg or \> 150 mmHg, and/or ventricular heart rate \< 80 bpm or \> 150 bpm. For subjects to meet eligibility criteria, at least 2 of the 3 measurements of vital signs during screening (45, 30, and/or 15 minutes prior to dosing) must meet criteria.
• Current AF episode treated with Class I or Class III antiarrhythmic drugs or electrical cardioversion. Subjects whose current AF episode has been treated with flecainide are eligible if their total cumulative exposure to flecainide (including the study drug to be administered in this study) does not exceed 320 mg within a 24-hour period, per site standard of care.
• History of acute decompensated heart failure (HF)
• History within 6 months prior to screening of, or present HF with a left ventricular ejection fraction (LVEF) \< 45%, and/or Class II or higher HF as defined by the New York Heart Association (NYHA), and/or medication history suggestive of HF, in the opinion of the Investigator. An echocardiogram with LVEF within 6 months of screening is required to demonstrate eligibility. If no echocardiogram is available, subject must undergo a diagnostic echocardiogram using a portable handheld ultrasound device (handheld echocardiogram; HHE) during screening to confirm eligibility.
• Evidence of current ongoing myocardial ischemia, such as signs (e.g., significant \[e.g., \> 2 mm\] ST segment elevation or depression on ECG, echocardiographic findings suggestive of acute myocardial infarction), symptoms (e.g., angina pectoris, atypical angina pectoris), and/or being medicated with anti-anginal medication. In addition, subjects with signs of prior myocardial infarction (such as pathological Q waves) who are also taking concomitant medications for angina pectoris should be evaluated for presence of ongoing ischemia.
• History of myocardial infarction (MI) within 3 months of screening
• Known uncorrected severe aortic or mitral stenosis
• Hypertrophic cardiomyopathy with outflow tract obstruction
• Current diagnosis of persistent AF
• One or more episodes of atrial flutter within 6 months prior to screening or atrial flutter at presentation
• History of any of the following heart abnormalities:
• Long QT syndrome
• Conduction disease (e.g. second- or third- degree heart block, bundle brach block)
• Diagnosed with sinus node dysfunction (e.g., sick sinus syndrome) and/or one of the following:

Sponsors & Collaborators

• InCarda Therapeutics, Inc.: lead

Study Sites (9)

Imelda

Bonheiden, Belgium

Location

OLVG

Amsterdam, Netherlands

Location

Deventer Ziekenhuis

Deventer, Netherlands

Location

Admiraal De Ruyter Ziekenhuis

Goes, Netherlands

Location

UMCG

Groningen, Netherlands

Location

Spaarne Gasthuis

Haarlem, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Gelre Ziekenhuizen

Zutphen, Netherlands

Location

Isala Klinieken

Zwolle, Netherlands

Location

Related Publications (2)

• Ruskin JN, Camm AJ, Dufton C, Woite-Silva AC, Tuininga Y, Badings E, De Jong JSSG, Oosterhof T, Aksoy I, Kuijper AFM, Van Gelder IC, van Dijk V, Nuyens D, Schellings D, Lee MY, Kowey PR, Crijns HJGM, Maupas J, Belardinelli L; INSTANT Investigators. Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial. JACC Clin Electrophysiol. 2024 Jun;10(6):1021-1033. doi: 10.1016/j.jacep.2024.02.021. Epub 2024 Apr 10.

  PMID: 38613545 DERIVED

• Crijns HJGM, Elvan A, Al-Windy N, Tuininga YS, Badings E, Aksoy I, Van Gelder IC, Madhavapeddi P, Camm AJ, Kowey PR, Ruskin JN, Belardinelli L; INSTANT Investigators*. Open-Label, Multicenter Study of Flecainide Acetate Oral Inhalation Solution for Acute Conversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm. Circ Arrhythm Electrophysiol. 2022 Mar;15(3):e010204. doi: 10.1161/CIRCEP.121.010204. Epub 2022 Feb 24.

  PMID: 35196871 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Flecainide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: VP Clinical Operations
• Organization: InCarda Therapeutics

propst.meisa@incardatherapeutics.com

510-422-5522

Study Officials

• Luiz Belardinelli, MD

  Chief Medical Officer at InCarda Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Part A was open-label however subjects were randomized to either a single dose or a double dose. There was no masking and this was a single-arm study. Part B was an open-label, multicenter design to confirm the safety (including tolerability) and efficacy of the optimal dose from Part A. Part C was an open-label, multicenter design study to assess the feasibility of self-administration of FlecIH-103 under medical supervision. Part C also included a sub-study to evaluate a hand-held echocardiogram device to assess the feasibility of its use in an emergent setting.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The 3 parts of the study were performed sequentially. Only Part A was randomized to assign subjects to either the 30 mg dose or 60 mg. Parts B and C were not randomized. There were no comparators in this study and no masking.

Study Record Dates

• First Submitted: February 26, 2018
• First Posted: May 29, 2018
• Study Start: May 29, 2018
• Primary Completion: January 17, 2022
• Study Completion: January 17, 2022
• Last Updated: May 14, 2024
• Results First Posted: May 14, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); NL (8)