Placebo: The formulation of placebo will consist of water, sodium acetate, disodium EDTA, and sulfuric acid to reproduce the same pH as the etripamil formulation.
Etripamil: The formulation of etripamil is for IN administration and will consist of etripamil, water, acetic acid, disodium ethylene-diamine-tetra-acetic acid (EDTA), and sulfuric acid. The dose of etripamil to be evaluated in this study is 70 mg with an optional second dose of 70 mg 10 minutes after the first dose if symptoms persist.
Study summary
This is a multi-national, multi-center, randomized, double-blind, placebo-controlled study to evaluate the effects of etripamil NS in patients with atrial fibrillation (AF). This study includes Screening Visit, Randomization Visit, a Treatment Period with scheduled Follow-up Visits (Monthly Follow-up and Post-treatment Follow-up Visits), a Final Study Visit, and an End of Study Telephone Follow up Visit.
Each patient will be randomized 1:1 to receive placebo or 70 mg Etripamil NS regimens. Patients will self-administer study drug for a perceived episode of AF with RVR with an initial dose of placebo or 70 mg etripamil NS, followed by an optional second dose of the same study drug 10 minutes after the first dose if the patient continues to experience symptoms. Patients may treat up to a maximum of 4 episodes in the study.
Informed consent will be obtained prior to any study procedures.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Age 18 years and over.
2. Provision of written informed consent.
3. Documented history of symptomatic AF (paroxysmal, persistent, or permanent) with a ventricular rate of ≥110 bpm.
* Documentation: electrocardiogram (ECG) tracing (including 12-lead ECG or ECG strip) showing AF with ventricular rate ≥110 beats per minute (bpm). This ECG documentation (anonymized with study Patient ID only) will be submitted to the Sponsor after screening and prior to randomization to confirm diagnosis of AF with RVR and eligibility to be randomized in the study. Patients who have undergone a prior ablation procedure for AF or for an AF-trigger must have documented AF with RVR post-ablation for study eligibility.
4. Documented history of repeated (at least 2 within the prior 12 months) and prolonged (at least 20 minutes) symptomatic episodes of AF with elevated (perceived or measured) heart rate (HR).
* Documentation: Patient description, other history, or medical records. Patients who have undergone a prior ablation procedure for AF or for an AF-trigger must fulfill this criterion post-ablation for study eligibility.
5. Receiving appropriate antithrombotic/anticoagulation therapy as per applicable national and/or local guidelines for AF management.
6. Women of childbearing potential must have a negative pregnancy test at Screening and agree to use at least 1 highly effective form of contraception from time of randomization until 7 days after the last administration of study drug and must be willing to discontinue from the study should they become or plan to become pregnant.
Exclusion Criteria:
1. Patients with a primary diagnosis of atrial flutter (typical or atypical) or atrial tachycardia. Patients with AF who have been observed to also experience atrial flutter within the same episode (i.e., "AFib/Flutter" or an admixture of AF and flutter within the same episode) are eligible.
2. History of any of the following within the last 6 months: Class 3 or 4 angina per Canadian Cardiovascular Society (CCS) criteria; ischemic chest pain during AF episodes; acute coronary syndrome, unless the patient has been successfully revascularized; coronary artery bypass grafting or open-chest valve surgery.
3. History of heart failure (HF) New York Heart Association (NYHA) classification ≥Class III within the last 3 months.
* The etiology of any HF should have been previously evaluated and addressed.
* HF with a reduced ejection fraction and/or HF with a preserved ejection fraction are acceptable.
4. History of hemodynamic instability during AF, i.e., symptoms or signs of severe hypotension, or syncope due to a pause upon conversion from AF to sinus rhythm (SR).
5. History of unexplained syncope.
6. History of, or ECG evidence at the screening visit, of: sick sinus syndrome, Mobitz II second- or third-degree atrioventricular (AV) block bradycardia (\<40 bpm) or pauses \>3 seconds during waking hours, without a pacemaker.
7. History of, or ECG evidence at the Screening visit, of: torsades de pointes, ventricular fibrillation, or ventricular tachycardia, Brugada syndrome, an antegrade conducting accessory bypass tract (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndromes), or long QT syndrome.
8. History of stroke, transient ischemic attack or peripheral embolism within the last 3 months.
9. CHA2DS2-VASc score of \>5.
10. Planned AF or AV node ablation within the next 3 months.
11. Uncorrected, severe aortic or mitral stenosis.
12. Hypertrophic cardiomyopathy with outflow tract obstruction.
13. History of sensitivity to verapamil or to any components of the investigational product.
14. History of recent or current chronic alcohol or drug abuse that, in the opinion of the Investigator, could impact the validity of the study results.
15. Currently participating in another drug or device study, or has received an investigational drug or device within 30 days prior to Screening.
16. Any other significant co-morbid condition that may negatively impact the patient's participation in the study or likely result in non-compliance.
Primary outcome measure(s)
Demonstrate the efficacy of etripamil NS over placebo in patients with AF. — 30 minutes from first drug administration The maximum reduction in ventricular rate, measured from ECG CMS recordings, within 30 minutes from first drug administration
Trial sites (11)
Facility
City
Region
Status
Interventional Cardiology Medical Group (West Hills, CA)
West Hills
California
Recruiting
South Denver Cardiology Associates P.C
Littleton
Colorado
Recruiting
Cardiovascular Associates Of The Delaware Valley
Haddon Heights
New Jersey
Recruiting
Weill Cornell Medicine
Manhattan
New York
Recruiting
Montreal Heart Institute
Montreal
Quebec
Recruiting
Rijnstate Ziekenhuis
Arnhem
Gelderland
Recruiting
Bravis ziekenhuis
Roosendaal
North Brabant
Recruiting
Noordwest Ziekenhuisgroep
Alkmaar
North Holland
Recruiting
ZGT
Almelo
Overijssel
Recruiting
Ikazia Ziekenhuis
Rotterdam
South Holland
Recruiting
Frisius Medisch Centrum
Friesland
Netherlands
Recruiting
More Milestone Pharmaceuticals Inc. trials in Canada
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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