Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia. NODE-303

Study Overview
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Brief Summary
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NODE-303 is a multi-center, open label (OL) study to evaluate the safety of etripamil NS in patients with Paroxysmal Supraventricular Tachycardia (PSVT). Patients will be provided with an ambulatory Cardiac Monitoring System (CMS) to help document PSVT episodes. The CMS will be self-applied by the patient, when they feel the onset of PSVT symptoms. Patients will self-administer etripamil NS if vagal maneuver is ineffective. After an episode of PSVT where drug is administered, the patient will return to the investigative site and have the option to continue in NODE-303 and manage subsequent episodes of PSVT with etripamil NS.

Detailed Description
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NODE-303 is a multi-center, open label (OL) study to evaluate the safety of etripamil NS in patients with Paroxysmal Supraventricular Tachycardia (PSVT). Patients will be provided with an ambulatory Cardiac Monitoring System (CMS) to help document PSVT episodes. The CMS will be self-applied by the patient, when they feel the onset of PSVT symptoms. Patients will self-administer etripamil NS if vagal maneuver is ineffective. After an episode of PSVT where drug is administered, the patient will return to the investigative site and have the option to continue in NODE-303 and manage subsequent episodes of PSVT with etripamil NS. The study will include: A Screening Visit during which the Investigator will verify that the patient meets the eligibility criteria of the NODE-303 study, will obtain the signed informed consent, take blood and urine for laboratory evaluations, and conduct other screening procedures. The informed consent for NODE-303 will be applicable for the initial and all subsequent PSVT episodes. A Baseline Visit during which the site will confirm eligibility, concomitant medications, train the patient on study procedures, and give the patient study drug, patient reported outcome (PRO) materials, and the CMS materials. A Treatment Period during which the patient will complete the monthly PRO survey, self-identify symptoms of PSVT, use the CMS, perform a vagal maneuver (VM), and self-administer etripamil NS if the symptoms do not resolve during or after the VM. Patients may be contacted during this period for reminders and training on what to do during a PSVT episode. Patients will also complete a per episode survey after any PSVT episode they experience. During the Treatment Period, Follow-up Visits will occur at the study site up to 14 days after each episode of PSVT which is treated with etripamil NS, and during which the Investigator will evaluate the results of the last usage of etripamil NS and reassess patient's eligibility to continue in the study based on study inclusion and exclusion criteria. Patients who are eligible to continue in the study will receive two additional kits containing study medication. A Final Study Visit that will occur when a patient discontinues or withdraws from the study, or when the overall study is completed, or the patient has completed the maximum number of doses. NODE-303 will continue until enough documented self-administrations of etripamil NS are included in the safety database to meet regulatory requirements for the etripamil NS development program. The common study end date (CSED) for the entire study will depend on the rate of accrual of the primary endpoint, unique patients with an episode. When the criteria for concluding the study have been met, the Sponsor will announce the common study end date (CSED) for the entire study and sites will be informed in advance to schedule all final patient visits prior to the CSED.

Official Title
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The NODE-303 Study: Multi-Centre, Multi-National,Open Label, Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia.

Conditions
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Paroxysmal Supraventricular Tachycardia

Intervention / Treatment
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* Drug: Etripamil NS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A patient will be eligible for study participation if they meet all of the following criteria: Has been diagnosed with PSVT by a medical professional, and reports having at least one previous episode of PSVT. For clarity, PSVT refers to episodic Supraventricular Tachycardia (SVT) that includes the atrioventricular (AV) node as a critical part of reentrant circuit. Is at least 18 years of age; Signed NODE-303 written informed consent Women of child-bearing potential must be willing to use at least 1 form of contraception during the trial, and must be willing to discontinue from the study should they become or plan to become pregnant.Postmenopausal females are defined as having amenorrhea for at least 12 months prior to Screening without an alternative medical cause. Willing and able to comply with study procedures Exclusion Criteria: A patient will be excluded from the study if they meet any of the following criteria: Patients with only a history of atrial arrhythmia that does not involve the atrioventricular (AV) node as part of the tachycardia circuit (e.g. atrial fibrillation, atrial flutter, intra-atrial tachycardia) are not eligible. Patients with a history of these tachycardias who are also diagnosed with PSVT are eligible. History of allergic reaction to verapamil Current therapy with digoxin, or any Class I or III antiarrhythmic drug. Patients may be eligible if these drugs are stopped at least five half-lives before the administration of etripamil NS. The only exception is amiodarone which must be stopped 30 days before enrollment. History or evidence of ventricular pre-excitation, e.g., delta waves, Wolff- Parkinson-White syndrome History or evidence of a second- or third-degree AV block History or evidence of severe ventricular arrhythmia (e.g., torsades de pointes, ventricular fibrillation, or sustained ventricular tachycardia). Symptoms of congestive heart failure New York Heart Association Class II to IV SBP < 90 mmHg at Screening, Baseline or any Follow-up Visit. Severe symptoms of hypotension experienced during PSVT episodes. Significant physical or psychiatric condition including alcoholism or drug abuse, which, in the opinion of the Investigator, could jeopardize the safety of the patient, or impede the patient's capacity to follow the study procedures History of syncope due to an arrhythmic etiology at any time, or history in last 5 years of unexplained syncope Is pregnant or breastfeeding Previously enrolled in a clinical trial for etripamil and received study drug or participation in any clinical trial for other investigational products or medical devices within 30 days of Screening. History of Acute Coronary Syndrome (ACS) or stroke within 6 months of screening Evidence of renal dysfunction as determined by an estimated glomerular filtration rate assessed at the Screening Visit as follows: <60mL/min/1.73m2 for patients <60 years of age; <40mL/min/1.73m2 for patients ≥60 and <70 years of age <35mL/min/1.73m2 for patients ≥70 years of age

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etripamil NS 70mg<br>Patients will self-administer etripamil NS. | Drug: Etripamil NS<br>* Patients will be provided with an ambulatory Cardiac Monitoring System (CMS) to help document PSVT episodes. The CMS will be self-applied by the patient, when PSVT symptoms begin. Patients will self-administer etripamil NS if vagal maneuver is ineffective. After an episode of PSVT where drug is administered, the patient will return to the investigative site for a study visit and will be given the option to continue in NODE-303 and manage subsequent episodes of PSVT with etripamil NS.<br>* Other names: MSP-2017;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of etripamil NS 70mg for the patient-administered treatment of acute episodes of PSVT outside of the clinical setting. | Measured by: Number of participants presenting Adverse Events and/or Number of participants with abnormal findings from the CMS recordings and physical examinations. | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of etripamil NS 70mg for the patient-administered treatment of acute episodes of PSVT outside of the clinical setting measured by median time to conversion post etripamil NS administration |  | 10 Months | 
| Improvement in patient quality of life measured by the Treatment Satisfaction Questionnaire for Medication and/or the Patient Reported Outcomes (PRO) System . |  | 10 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSVT