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Trial record 1 of 1 for:    FLE-007
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Flecainide Acetate Inhalation Solution for Cardioversion of Recent-Onset, Symptomatic Atrial Fibrillation (RESTORE-1)

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ClinicalTrials.gov Identifier: NCT05039359
Recruitment Status : Recruiting
First Posted : September 9, 2021
Last Update Posted : April 28, 2022
Sponsor:
Information provided by (Responsible Party):
InCarda Therapeutics, Inc.

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).

Condition or disease Intervention/treatment Phase
Paroxysmal Atrial Fibrillation Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, double-blind, placebo controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 26, 2022
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : December 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: FlecIH-103 (flecainide acetate inhalation solution)
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: Placebo
Vehicle-matched inhalation solution

Placebo Comparator: Vehicle-matched inhalation solution (placebo)
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: Placebo
Vehicle-matched inhalation solution




Primary Outcome Measures :
  1. Assessment of proportion of patients whose AF converts using continuous ECG monitoring [ Time Frame: 90 minutes ]
    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.


Secondary Outcome Measures :
  1. Time of conversion to be monitored using continuous ECGs [ Time Frame: 90 minutes ]
    To compare the effects of flecainide acetate inhalation solution and placebo on the time to conversion of AF to SR. Conversion from AF to SR will be monitored via continuous ECG recording. The time of conversion as captured on the continuous ECG will be compared between flecainide acetate inhalation solution and placebo.

  2. Assessing and comparing the AF related symptoms by using a questionnaire [ Time Frame: 90 minutes post dose ]
    To compare the effects of flecainide acetate inhalation solution and placebo on the AF-related symptoms. The AF-related symptoms will be reported by the patients in the AF-Related Symptoms Questionnaire at 90 minutes after initiation of dosing.

  3. Assessing and comparing the hospital admissions between the active vs. placebo [ Time Frame: 90 minutes ]
    To compare the effects of flecainide acetate inhalation solution and placebo on the patient hospitalizations prior to discharge as reported by the investigator in the CRF.

  4. Assessing and comparing the AF-related interventions prior to discharge between the active vs. placebo [ Time Frame: 90 minutes ]
    To compare the effects of flecainide acetate inhalation solution and placebo on the AF-related interventions as reported by the investigator in the CRF.

  5. Assessing and comparing the time of discharge [ Time Frame: 90 minutes ]
    To compare the effects of flecainide acetate inhalation solution and placebo on the time to discharge as reported by the investigator in the CRF.



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ≥18 and ≤85 years of age
  2. Recent onset of symptomatic newly diagnosed or paroxysmal AF

    1. Recent onset is defined as a symptom duration ≥1 and ≤48 hours at time of dosing
    2. Newly diagnosed AF is AF that has not been diagnosed previously, independent of its duration
    3. 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.
    4. A symptomatic recent-onset AF episode post cardiac ablation for paroxysmal AF would be considered eligible

Exclusion Criteria:

  1. History of non self-terminating AF/AFL as defined by

    1. One or more failed attempts to restore SR with pharmacological therapy
    2. 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
    3. More than 3 ECV procedures in ≤5 years prior to screening
  2. Current diagnosis of persistent AF

    1. 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
    2. Patients who have undergone an ablation procedure for persistent AF are not eligible
  3. 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

  4. Hemodynamic or cardiac instability during AF, defined as any of the following:

    1. Systolic blood pressure <100 or ≥160 mmHg
    2. Diastolic blood pressure ≥95 mmHg
    3. Ventricular heart rate <80 or >160 bpm
  5. Respiratory rate >22 breaths per minute Relevant structural heart disease
  6. History of decompensated heart failure (HF)
  7. 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) <45% i. For patients in the United States, a standard diagnostic echocardiogram assessed ≤180 days prior to screening is required to ascertain eligibility. If none is available, the patient must undergo a standard diagnostic echocardiogram or a diagnostic echocardiogram using a portable ultrasound device (handheld echocardiogram [HHE]) during screening to confirm eligibility c. New York Heart Association (NYHA) Class II-IV symptoms d. Medication history suggestive of HF per the Investigator's discretion

  8. Signs or symptoms of ongoing myocardial ischemia, including any of the following:

    1. Significant ST segment elevation or depression (ie, ≥2 mm) on a standard 12-lead ECG
    2. Echocardiogram findings (eg, wall motion abnormalities) suggestive of acute myocardial infarction (MI)
    3. Angina pectoris, atypical angina pectoris, or receiving antianginal medication for ischemia
  9. History of MI ≤3 months of screening
  10. History of uncorrected moderate or severe aortic or mitral valvular stenosis, in the opinion of the Investigator

    a. If an echocardiogram is performed at screening, moderate or severe valve disease observed during the examination is considered exclusionary

  11. History of LV hypertrophy with LV thickness >12 mm as observed in the most recent assessment, ie, an echocardiogram Other CV conditions
  12. Stroke (including transient ischemic attack) ≤3 months prior to randomization
  13. History of any of the following cardiac abnormalities:

    1. Long QT syndrome
    2. Conduction system disease (eg, PR interval >200 ms, second- or third degree heart block, bundle branch block)
    3. Brugada syndrome
    4. Torsade de pointes
    5. Diagnosed with sinus node dysfunction (eg, sick sinus syndrome) or any of the following:

    i. History of unexplained or cardiovascular syncope ii. Bradycardia suggestive of sinus node dysfunction iii. Prior electrical or pharmacological cardioversion associated with sinus or ventricular pause >3 seconds or ventricular heart rate <45 bpm at time of conversion

  14. Any of the following ECG-related features at screening:

    1. QT interval corrected for heart rate using the Fridericia formula (QTcF) >480 msec
    2. Wide QRS complex (ie, duration ≥120 msec) or history of documented wide QRS complex tachycardia (ie, wide QRS complex with ventricular heart rate >100 bpm)
    3. Presence of ventricular tachycardia (VT). Site telemetry should be equipped with an alarm system for VT and PVCs or be continuously visually observed prior to dosing
  15. Presence of a pacemaker
  16. Cardiac surgery for any of the exclusionary conditions (eg, valvular disease, hypertrophy, coronary artery disease) ≤6 months prior to randomization Prior and concomitant non-CV conditions
  17. Known severe renal impairment or patient receiving dialysis
  18. Known abnormal liver function, including hepatic disease or biochemical evidence of significant liver derangement
  19. Uncorrected hypokalemia

    1. Hypokalemia is defined as serum potassium below the normal range according to the local laboratory reference ranges at screening
    2. If serum potassium is below the normal range at screening, therapeutic correction (eg, potassium supplementation) is required
  20. Uncorrected hypomagnesemia

    1. Hypomagnesemia is defined as serum magnesium below the normal range according to the local laboratory reference ranges at screening
    2. If serum magnesium result is below the normal range at screening, therapeutic correction (eg, magnesium supplementation) is required
  21. Chronic obstructive pulmonary disease or other established pulmonary disease in need of inhalation medication

    a. Exception: patients with intermittent mild asthma who are not experiencing active symptoms at screening, and whose asthma is well controlled with as-needed administration of a bronchodilator ≤2 days/week, and who has not experienced ≥2 exacerbations requiring oral systemic corticosteroids ≤1 year prior to screening

  22. History of bronchospasm (eg, hyperreactive airways to inhalants) or difficulty inhaling medications
  23. Previous or current hospitalization for COVID-19, or any secondary cardiomyopathy from COVID-19 Prior and concomitant medications and procedures
  24. Treatment with Class I or III AADs ≤7 days prior to randomization
  25. Treatment with amiodarone ≤12 weeks prior to randomization
  26. Known hypersensitivity to flecainide acetate or any of its active metabolites Other
  27. Any condition or circumstance which in the opinion of the Investigator may make the patient unsuitable for the study, such as:

    1. High risk for stroke based on the screening coagulation panel or medical history per Investigator's discretion (eg, CHA2DS2-VASc score)
    2. Congenital heart disease
    3. AF that is secondary to electrolyte imbalance, thyroid disease, or other reversible or non-cardiovascular cause
    4. A serious or life-threatening medical condition
    5. An acute infection
  28. Known drug or alcohol dependence ≤12 months prior to screening as judged by the Investigator
  29. A body mass index >40 kg/m2
  30. Legally incompetent to provide informed consent
  31. Previous treatment with any other investigational drug ≤30 days from screening or 5 half-lives of the drug, whichever is longer
  32. Female of childbearing potential defined as any of the following:

    1. Not surgically sterile or postmenopausal (Appendix 1)
    2. A negative pregnancy test is unavailable at screening
    3. Pregnant or breastfeeding at screening Males whose sexual partners are women of childbearing potential (WOCBP) must use at least one highly effective method of contraception during the study unless permenantly sterile by bilateral orchiectomy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05039359


Contacts
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Contact: Meisa Propst 510-422-5522 ext 111 meisa@incardatherapeutics.com

Locations
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United States, California
Memorial Care Recruiting
Long Beach, California, United States, 90806
Contact: Emillie Chisholm    562-933-1106      
Principal Investigator: Mark Lee, MD         
Sponsors and Collaborators
InCarda Therapeutics, Inc.
Investigators
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Study Director: Luiz Belardinelli, MD InCarda Therapeutics, Inc.
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Responsible Party: InCarda Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05039359    
Other Study ID Numbers: FLE-007
First Posted: September 9, 2021    Key Record Dates
Last Update Posted: April 28, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by InCarda Therapeutics, Inc.:
atrial fibrillation
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes