ReVeRA-201: Etripamil in Atrial Fibrillation, Phase 2

Milestone Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Atrial Fibrillation

Treatments: Drug: Etripamil; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04467905

MSP-2017-5001

Details and patient eligibility

About

Many patients with atrial fibrillation experience persistent tachycardia with episodes of rapid ventricular rate despite chronic treatment to reduce ventricular rate. The objectives of this study are to demonstrate the superiority of a nasal spray of etripamil over placebo, in reducing ventricular rate in patients with atrial fibrillation; and to evaluate the safety and efficacy of etripamil Nasal Spray in patients with atrial fibrillation (AF).

Full description

This is a multi-center, randomized, double-blind, placebo-controlled study to evaluate the effects of etripamil Nasal Spray in patients with atrial fibrillation (AF). This study includes Screening, the Treatment Period (Screening and Treament Period occur on the same day) and Follow-up procedures.

Each patient will receive placebo or 70 mg of etripamil intranasally; treatment will be randomized in a 1:1 ratio, to yield 50 evaluable patients with atrial fibrillation in 2 groups of 25.

Patients with atrial fibrillation (AF) will be selected by the Investigator. The screening procedures will include obtaining informed consent, a review of inclusion/exclusion criteria, a complete physical examination, and recording of any concomitant medications.

After screening procedures are complete, eligible patients will be randomized to receive etripamil or placebo. Heart rate will be measured via Holter ECG (Electrocardiogram)10 minutes prior to and immediately before drug administration; patients must exhibit a rapid ventricular rate (≥110 bpm measured during 1 minute) on the Holter report prior to drug administration in order to receive the study drug. Blinded study drug will be administered during Holter ECG (Electrocardiogram) monitoring, which will be conducted for at least 10 minutes prior to and for 6 hours after administration, patient discharged after 60 minutes if clinically warranted.

Patients will undergo a safety follow-up assessment and return the Holter device approximately 24 hours post-dose. Patients will also be contacted by phone 7 days post-dosing for safety follow-up.

Enrollment: 69 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

A patient will be eligible for study participation if they meet all of the following criteria:

1. Aged 18 years and over.

2. Has provided written informed consent.

3. Patients with episodes of paroxysmal, persistent or permanent AF (Atrial Fibrillation), presenting with AF and a ventricular rate ≥110 bpm, measured over 1 minute

4. Patients should receive appropriate antithrombotic therapy as per the applicable guidelines for atrial fibrillation management (e.g., Canadian Cardiovascular Society (CCS) guidelines / European Society of Cardiology (ESC) guidelines).

   1. Etripamil (a calcium channel blocker) is intended for acute rate control only. If rhythm control is desired (outside of the present protocol), anticoagulation as per guidelines may start after the administration of study drug.

Exclusion criteria

A patient will be excluded from the study if they meet any of the following criteria:

1. Has evidence of atrial flutter (ECG) at presentation.
2. Has a history of stroke,Transient Ischemic Attack (TIA) or peripheral embolism within the last 3 months.
3. Has received by IV route any of the following within one hour before study drug administration: flecainide, procainamide, digoxin, beta-blocker, or calcium channel blocker.
4. Has signs and symptoms of severe congestive heart failure at presentation (e.g. tachypnea, oxygen desaturation <90% unless due to known pulmonary disease, pulmonary rales, sign of peripheral hypoperfusion).
5. Hemodynamic instability, with systolic blood pressure <90 mmHg or diastolic blood pressure <60 mmHg.
6. Known uncorrected severe aortic or mitral stenosis.
7. Hypertrophic cardiomyopathy with outflow tract obstruction.
8. Has a history of second- or third-degree atrioventricular block.
9. Regular rhythm suggesting a complete Atrioventricular (AV) block.
10. Has a history or evidence of torsades de pointes, sick sinus syndrome, or Brugada syndrome.
11. Evidence of Acute Coronary Syndrome within the last 12 months except if patient was successfully revascularized.
12. Positive pregnancy test result at screening, and females of childbearing potential who do not agree to use adequate method of contraception for the duration of the study.
13. Has evidence of any clinically significant acute or chronic condition of the nasal cavity (e.g., rhinitis or deviated septum) which could interfere with administration of the study drug in either or both nasal cavities.
14. Has a history of sensitivity to verapamil.
15. Has previously participated in a clinical study for etripamil.
16. Has a history of sensitivity to any components of the investigational product.
17. Signs of alcohol or drug intoxication at the time of presentation which, in the opinion of the Investigator, would impact the validity of study results.
18. Is currently participating in another drug or device study, or has received an investigational drug or device within 30 days of Screening.
19. Has evidence of clinically significant cardiovascular, endocrine, gastrointestinal, hematologic, hepatic, immunologic, neurologic, oncologic, pulmonary, psychiatric, or renal disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the patient or impact the validity of study results.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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69 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Patients will receive a total of 200 μL of placebo ((i.e. 100 μL in each nostril) via the Aptar Pharma Nasal Spray Bidose System. The devices will be prefilled and packaged. Instructions on device usage will be provided.

Treatment:

Drug: Placebo

Etripamil

Experimental group

Description:

Patients will receive a total of 200 μL of etripamil Nasal spray 70 mg via the Aptar Pharma Nasal Spray Bidose System. The devices will be prefilled and packaged. Instructions on device usage will be provided.

Treatment:

Drug: Etripamil