Ignite Creation Date:
2025-12-24 @ 3:02 PM
Ignite Modification Date:
2025-12-27 @ 11:44 PM
Study NCT ID:
NCT05039359
Status:
TERMINATED
Last Update Posted:
2023-10-30
First Post:
2021-08-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Flecainide Acetate Inhalation Solution for Cardioversion of Recent-Onset, Symptomatic Atrial Fibrillation
Sponsor:
InCarda Therapeutics, Inc.
Organization:
Study Overview
Official Title:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial of Flecainide Acetate Inhalation Solution for Cardioversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm
Status:
TERMINATED
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Limited efficacy upon blinded review
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RESTORE-1
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).
Detailed Description:
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. The study will consist of the following periods: Screening, Observation, and Follow-up.
The Screening Period comprises the time from the patient signing informed consent to the time of randomization. Screening begins at least 45 minutes prior to dosing and may be extended as needed due to site logistics. During screening, the patient will be evaluated for study eligibility, have a standard triplicate 12-lead ECG to confirm the diagnosis of AF, have a single-lead patch electrode applied for continuous ECG (cECG) recording, undergo a targeted physical examination (including cardiovascular and respiratory systems), have blood drawn for laboratory assessments and a predose pharmacokinetic (PK) sample, have their AF-related symptoms assessed, have vital signs assessed periodically, and be monitored via telemetry to ensure they remain predominantly in AF prior to dosing (ie, no period of SR ≥1 minute in duration or any abnormal rhythm other than AF). After confirmation that the patient meets all applicable eligibility criteria, randomization will take place using a central randomization system. The patient is considered enrolled at the time of randomization.
The Observation Period comprises the time from randomization through 90 minutes after initiation of dosing. After randomization and just prior to the start of dosing (T0), the patient's AF will again be confirmed by a standard triplicate 12-lead ECG; patients who are not in AF at this time must be withdrawn. The patient will inhale the study drug until conversion of AF to SR occurs for ≥1 minute or the complete dose is administered, whichever occurs first. The complete dose of study drug comprises 2 separate 3.5-minute inhalations separated by a 1-minute break. Telemetric recording of ECG and cECG monitoring will continue and vital signs will be monitored periodically. A PK sample will be collected 2 minutes after completion of dosing followed by another standard triplicate ECG collected 5 minutes after completion of dosing. Finally, AF-related symptoms will be checked and a final PK sample will be collected at 90 minutes after initiation of dosing. Wherever a time point requires collection of ECG and/or vital signs in addition to a PK sample, the PK sample is collected last.
If the patient's AF converts to SR (sustained for ≥1 minute) as observed on telemetry during the Observation Period, vital signs and a standard triplicate 12-lead ECG will be recorded immediately following the time of conversion. The Investigator may not offer the patient another rhythm control therapy to cardiovert their AF to SR until after 90 minutes after initiation of dosing. At the end of the Observation Period (ie, 90 minutes after initiation of dosing), the cECG patch will be removed and a standard triplicate 12 lead ECG will be recorded. If the patient's AF converts to SR (sustained for ≥1 minute) after the Observation Period but prior to discharge (eg, due to ECV or other PCV), a standard triplicate 12-lead ECG will be recorded at the time of conversion.
The patient may be discharged per the Investigator's discretion any time after completion of the 90-minute time point assessments. If patient discharge occurs \>1 hour after completion of the last 90-minute time point assessment, all 90-minute time point assessments must be repeated just prior to discharge, excluding the PK sample.
The Follow-Up Period consists of 2 follow-up telephone contacts: one at 24 (+12) hours after initiation of dosing, and one at 96 (±24) hours after initiation of dosing. The patient will also be given contact information and be instructed to contact the clinic in the event that any AF-related symptoms occur before these scheduled contact times. Follow-up contacts may also be performed by video call or in-person if the patient is at the clinic. During each follow-up contact, the patient will be queried for concomitant medications and procedures, AEs, AF-related symptoms, and AF-related interventions. End of study coincides with the 96-hour follow-up contact.
An independent Data Monitoring Committee (DMC) will monitor safety throughout the study. An independent Clinical Events Committee (CEC) will review blinded data to adjudicate the primary and several secondary efficacy endpoints and to adjudicate CV events of special interest (ie, hypotension, ventricular tachycardia, bradycardia, sinus pause, atrial flutter with 1:1 conduction, and other arrhythmias).
The Screening Period comprises the time from the patient signing informed consent to the time of randomization. Screening begins at least 45 minutes prior to dosing and may be extended as needed due to site logistics. During screening, the patient will be evaluated for study eligibility, have a standard triplicate 12-lead ECG to confirm the diagnosis of AF, have a single-lead patch electrode applied for continuous ECG (cECG) recording, undergo a targeted physical examination (including cardiovascular and respiratory systems), have blood drawn for laboratory assessments and a predose pharmacokinetic (PK) sample, have their AF-related symptoms assessed, have vital signs assessed periodically, and be monitored via telemetry to ensure they remain predominantly in AF prior to dosing (ie, no period of SR ≥1 minute in duration or any abnormal rhythm other than AF). After confirmation that the patient meets all applicable eligibility criteria, randomization will take place using a central randomization system. The patient is considered enrolled at the time of randomization.
The Observation Period comprises the time from randomization through 90 minutes after initiation of dosing. After randomization and just prior to the start of dosing (T0), the patient's AF will again be confirmed by a standard triplicate 12-lead ECG; patients who are not in AF at this time must be withdrawn. The patient will inhale the study drug until conversion of AF to SR occurs for ≥1 minute or the complete dose is administered, whichever occurs first. The complete dose of study drug comprises 2 separate 3.5-minute inhalations separated by a 1-minute break. Telemetric recording of ECG and cECG monitoring will continue and vital signs will be monitored periodically. A PK sample will be collected 2 minutes after completion of dosing followed by another standard triplicate ECG collected 5 minutes after completion of dosing. Finally, AF-related symptoms will be checked and a final PK sample will be collected at 90 minutes after initiation of dosing. Wherever a time point requires collection of ECG and/or vital signs in addition to a PK sample, the PK sample is collected last.
If the patient's AF converts to SR (sustained for ≥1 minute) as observed on telemetry during the Observation Period, vital signs and a standard triplicate 12-lead ECG will be recorded immediately following the time of conversion. The Investigator may not offer the patient another rhythm control therapy to cardiovert their AF to SR until after 90 minutes after initiation of dosing. At the end of the Observation Period (ie, 90 minutes after initiation of dosing), the cECG patch will be removed and a standard triplicate 12 lead ECG will be recorded. If the patient's AF converts to SR (sustained for ≥1 minute) after the Observation Period but prior to discharge (eg, due to ECV or other PCV), a standard triplicate 12-lead ECG will be recorded at the time of conversion.
The patient may be discharged per the Investigator's discretion any time after completion of the 90-minute time point assessments. If patient discharge occurs \>1 hour after completion of the last 90-minute time point assessment, all 90-minute time point assessments must be repeated just prior to discharge, excluding the PK sample.
The Follow-Up Period consists of 2 follow-up telephone contacts: one at 24 (+12) hours after initiation of dosing, and one at 96 (±24) hours after initiation of dosing. The patient will also be given contact information and be instructed to contact the clinic in the event that any AF-related symptoms occur before these scheduled contact times. Follow-up contacts may also be performed by video call or in-person if the patient is at the clinic. During each follow-up contact, the patient will be queried for concomitant medications and procedures, AEs, AF-related symptoms, and AF-related interventions. End of study coincides with the 96-hour follow-up contact.
An independent Data Monitoring Committee (DMC) will monitor safety throughout the study. An independent Clinical Events Committee (CEC) will review blinded data to adjudicate the primary and several secondary efficacy endpoints and to adjudicate CV events of special interest (ie, hypotension, ventricular tachycardia, bradycardia, sinus pause, atrial flutter with 1:1 conduction, and other arrhythmias).
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: