ReVeRA-301: Etripamil in Atrial Fibrillation Phase 3

This is a multi-national, multi-center, randomized, double-blind, placebo-controlled study to evaluate the effects of etripamil NS in patients with AF. This study includes a Screening Visit, Randomization Visit, Treatment Period with Follow-up Visits (Monthly Follow-up Visits, and Post-treatment Follow-up Visits), a Final Study Visit, and an End of Study Telephone Follow-up Visit.

Each patient will be randomized in a 1:1 ratio to receive Placebo or 70 mg Etripamil NS regimens. Patients will self-administer study drug for a perceived episode of AF with RVR as follows: an initial dose of placebo or 70 mg etripamil NS, followed by an optional second dose 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 must be obtained prior to any study procedures.

Screening Visit:

Patients with a history of symptomatic AF with RVR will be selected by the Investigator. The screening procedures will include obtaining informed consent, a review of inclusion/exclusion criteria, vital signs, a physical examination, measuring height and weight, screening lab tests, 12-lead electrocardiogram (ECG), recording demographics and medical history and recording of any concomitant medications.

Documentation of AF with RVR, and other data if relevant or requested (e.g. concomitant medications, medical history) will be submitted for Sponsor medical review to confirm and approve patient eligibility for randomization.

Randomization Visit:

Patients eligible for randomization will return to the site to confirm eligibility, record any changes in concomitant medications and adverse events (AEs), and receive training in study procedures including recognizing the presence of customary symptoms of AF, use of the ECG cardiac monitoring system (CMS) device, and electronic patient reported outcome (ePRO) device. Patients will then be randomized 1:1 to placebo or etripamil NS and dispensed study drug kits.

Treatment Period:

When randomized patients identify symptoms of an episode of AF with RVR, they will perform a sequence of steps, including affixing an ECG CMS device, confirming they have an elevated ventricular rate (≥110 bpm), self-administering study drug, and completing an ePRO at specified times post-study drug. A caregiver may help the patient with these procedures. Administration of the study drug regimen during an AF episode is as follows: an initial dose of study drug followed by an optional second dose 10 minutes after the first dose if symptoms persist.

Patients should refrain from additional treatment for their AF with RVR until 45 minutes after their first dose of study drug, after which they should treat their episode as needed per physician-recommended standards of care.

A patient may treat up to 4 episodes during the study.

Follow-up Visits:

Monthly Follow-up Visits Follow-up Visits will occur approximately monthly from the time of randomization until the patient completes the study. These visits will be conducted via site visit or telephone. AEs and concomitant medications therapies will be collected and recorded, continued patient eligibility will be assessed based on information collected, and any re-training on study procedures will be conducted.

Post-treatment Follow-up Visit(s) A Post-treatment Follow-up Visit will occur at the study site within 14 days after a patient administers study drug during the Treatment Period. Up to 4 treated episodes of perceived AF are allowed per patient. AEs and concomitant medications will be collected and recorded, weight and vital signs will be measured, the CMS report from the treated episode will be reviewed, patient eligibility confirmed, study drug kits will be collected for drug accountability, and if applicable the patient will be re-randomized and additional study drug kits dispensed. A focused physical examination will also be performed if needed to assist in the evaluation of any reported AEs.

Details on any medical interventions (e.g. oral medication, intravenous [IV] medication, visits to the emergency department or health-care facility, and/or arrhythmia-related procedure [such as cardioversion]) associated with the treated episode will be collected.

If a patient has completed or will not be continuing in the study, Final Study Visit procedures will be performed.

Final Study Visit:

A Final Study Visit will occur at the study site after a patient administers study drug for the final time during the Treatment Period, or if the patient has completed participation in the study for any other reason. This Visit may be conducted at the same time as a Post-treatment Follow-up Visit.

AEs and concomitant medications will be collected and recorded, weight and vital signs will be measured, the CMS report from the treated episode will be reviewed. A focused physical examination will also be performed if needed to assist in the evaluation of any reported AEs. Reasons for study completion or withdrawal will be collected, and the patient will return the ECG monitoring device and ePRO device at this visit. Study drug kits, ECG CMS devices, and ePRO will be collected.

End of Study Telephone Follow-Up Visit:

An End of Study Telephone Follow-Up Visit will be completed approximately 30 days after the Final Study Visit to follow-up on any ongoing AEs. This visit is not required for patients who did not use the study drug within 30 days before their Final Study Visit.