Acute conversion to sinus rhythm (SR) in subjects with recent onset of symptomatic paroxysmal atrial fibrillation (AF). MedDRA version: 20.0 Level: LLT Classification code 10034039 Term: Paroxysmal atrial fibrillation System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Flecainide Acetate/35mg/ml (30mg eTLD)
Product Name: Flecainide Acetate
Product Code: FlecIH
Pharmaceutical Form: Oral solution/concentrate for nebuliser solution
INN or Proposed INN: Flec
Sponsors
InCarda Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Subjects with recent-onset symptomatic AF at presentation. 2) With a duration at onset of symptoms from 1 hour to 48 hours 3) And from one of the following categories: a) First detected episode of paroxysmal AF b) Recurrent episode of paroxysmal AF c) Episode post-cardiac ablation for paroxysmal AF 4)Part C Patient-Led Under Medical Supervision Cardioversion Study only: Subjects whose AF converted to SR with inhaled flecainide and without difficulties or issues with inhalation (in the opinion of the investigator), serious AE(s), or serious AESI(s) in Part A, Part B, or the Part C Medically-Led Cardioversion Study NOTE: 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 recentonset symptomatic AF. These subjects will be eligible to receive study drug only when presenting with symptomatic paroxysmal AF of recentonset (i.e., = 48 hours), consenting to the full study, and after meeting all eligibility criteria. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1) Subject 85 years of age 2) Hemodynamic and/or cardiac instability, with systolic blood pressure 150 mmHg, and/or ventricular heart rate 160 bpm. 3) 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 does not exceed 320 mg within a 24-hour period, per site standard of care. 4) History of acute decompensated heart failure (HF) 5)Evidence of significant HF defined as any of the following: a)Hospitalization in the last 12 months for HF or suspected HF event b)Most recent assessment of left ventricular ejection fraction (LVEF) 75 years old.2 d) Brugada Syndrome e) Torsades de pointes (TdP) 13) Any of the following ECG-related features: a) QTc interval > 480 msec at screening b) QRS duration = 120 ms or history of previous documented wide QRS tachycardia c) Predominantly (i.e., > 30 %) paced heart rhythm d) Ventricular tachycardia , or excessive premature ventricular complexes , prior to dosing as per site telemetry. Site telemetry should be equipped with an alarm system for VT and PVCs or be continuously visually observed prior to dosing 14) Severe renal impairment (eGFR < 30 mL/min/1.73 m2) or on dialysis 15)Known medical history of abnormal liver function prior to enrollment 16) Uncorrected hypokalemia (defined as serum potassium < 3.6 mEq/L) at screening. 17) Subjects with established pulmonary disease in need of inhalation medication. Subjects with COPD are excluded. Subjects with mild to moderate asthma that are not experiencing active symptoms at screening and whose asthma is well controlled with steroids and/or asneeded administration of a bronchodilator are eli
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): A: Feasibility is assessed in terms of the following performance characteristics: a) Rates of study enrollment, screen failures and refusals of IC; b) The rate of technically successful administration of the two study inhalation regimens; c) Successful capture of study data according to the schedule of study assessments; d) Successful remote capture of AF-status at follow-up contacts; B:The primary efficacy endpoint is the proportion of subjects whose AF converted to SR by inhaled flecainide within 90 minutes after initiation of dosing. C:-Proportion of subjects who achieved therapeutic dosing (= 200 ng/mL) with the study drug in the Part C Patient-Led Under Medical Supervision Cardioversion Study -Feasibility of patient-led self-administration of study drug, including: oPercent of subjects who consent to the study oPercent of subjects who withdraw from the study oPercent of subjects who are certified for self-administration of study drug oPercent of subjects who return to clinic with a recurrent episode of PAF within 8 months of signing consent, and the associated timeframe(s) to time(s) of recurrence oPercent of subjects that independently set up and inhale study drug according to the provided instructions -Proportion of subjects whose AF converted to SR -Proportion of subjects for whom capture and assessment of a diagnostic echocardiogram using a HHE at screening was successful -Percent of subjects who are considered ineligible for enrollment as a result of the HHE assessment -Time from HHE administration to availability of HHE report/results ;Timepoint(s) of evaluation of this end point: Time point specified in objectives;Main Objective: A: The main objective of Part A is to evaluate the feasibility of single and repeat administration of flecainide acetate inhalation solution (30, 60, 90 and 120 mg estimated total lung dose (eTLD) for acute conversion of recent onset of paroxysmal AF to SR. B: Efficacy objectiv | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints include: The proportion of subjects with Cmax values = 200 ng/mL (e.g., 200, 300, 400, and 500 ng/mL) post inhalation with inhaled flecainide (excluding plasma levels associated with IV flecainide infusion) whose AF converted to SR by inhaled flecainide within 90 minutes after initiation of dosing. - The time to conversion of AF to SR from initiation of dosing up to 60 minutes post dose; - The proportion of subjects in SR on Day 2; - The proportion of subjects with reduced or no AF symptoms at 30 minutes post dose; - The proportion of subjects with reduced or no AF symptoms at 60 minutes post dose; - The proportion of subjects with reduced or no AF symptoms at 90 minutes post dose; - The proportion of subjects who had their AF converted to SR within 90 minutes after initiation of dosing and had no AF recurrence, requiring electrical or pharmacological cardioversion or rate control intervention, up to discharge; - The proportion of subjects in SR on Day 5. Time to conversion will be reported in statistical analyses from both initiation of dosing and completion of dosing. Secondary safety endpoint: - Incidence of treatment emergent serious adverse events of interest for flecainide Exploratory endpoints (for Handheld Echo Sub-Study only): -Proportion of subjects for whom capture and assessment of a diagnostic echocardiogram using a HHE at screening was successful -Percent of subjects who are considered ineligible for enrollment as a result of the HHE assessment -Time from HHE administration to availability of HHE report/results ;Timepoint(s) of evaluation of this end point: Time point specified in objectives | — |
Countries
Belgium, Netherlands, United States
Contacts
Public ContactProject Manager Instant Study
Cardialysis BV
Outcome results
None listed