Efficacy and Safety Study of Etripamil Nasal Spray Self-Administration for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia

The study is a multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil NS self-administered by patients who experience an episode of PSVT in an at-home setting.

This is an event-driven study. Enrollment into the study will continue until the adjudication of the 180th positively adjudicated PSVT episode in patients treated with double-blind study drug during the Randomized Treatment Period required for the study's pivotal analysis. After the date of the adjudication of the 180th positively adjudicated PSVT episode, all randomized patients will be unblinded at this timepoint and enter into an approximately 6 months open-label period of the study.

Inclusion criteria

Patients who meet all of the following criteria will be eligible to participate in the study:

• Male or female patients at least 18 years of age;
• Electrographically documented history of PSVT (e.g., diagnosis based on ECG , Holter monitoring, etc.). If patient had a prior ablation for PSVT, patient must have documented ECG evidence of PSVT post-ablation;
• History of sustained episodes of PSVT (i.e., typically lasting 20 minutes or longer);
• Females of childbearing potential who are sexually active with a male partner who is not surgically sterile (i.e., vasectomy) must agree to use an approved highly effective form of contraception from the time of signed informed consent until 30 days after the last administration of study drug.;

The following categories define females who are NOT considered to be of childbearing potential:

• Premenopausal females with 1 of the following:

• Documented hysterectomy;
• Documented bilateral salpingectomy or tubal ligation; or
• Documented bilateral oophorectomy; or
• Postmenopausal females, defined as having amenorrhea for at least 12 months without an alternative medical cause; and
• Signed written informed consent.

Exclusion criteria

Patients who meet any of the following criteria will be excluded from participation in the study:

• Systolic blood pressure (SBP) <90 mmHg after a 5-minute rest in sitting position at the Screening Visit or before the test dose. In patients treated with a chronic prophylactic drug for PSVT (e.g., beta blockers, verapamil, and diltiazem), the drug may be stopped for at least the equivalent of 5 half-lives, patients may be rescreened once, and chronic use of the drug cannot be restarted after randomization;
• History of severe symptoms of hypotension, especially syncope, during episodes of PSVT;
• 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);
• History of allergic reaction to verapamil;
• Current therapy with digoxin or any Class I or III antiarrhythmic drug, except if these drugs are stopped at least the equivalent of 5 half-lives before the Test Dose Randomization Visit;
• Current chronic therapy with oral amiodarone, or have taken oral amiodarone within 30 days prior to the Test Dose Randomization Visit;
• Evidence of ventricular pre-excitation (e.g., delta waves, short PR interval <100 msec, Wolff Parkinson White syndrome) on the ECG performed at the Screening Visit or before the test dose administration;
• Evidence of a second- or third-degree AV block on the ECG performed at the Screening Visit or before the test dose administration;
• History or evidence of severe ventricular arrhythmia (e.g., torsades de pointes, ventricular fibrillation, or ventricular tachycardia);
• Current congestive heart failure defined by the New York Heart Association Class II to IV;
• History of Acute Coronary Syndrome or stroke within 6 months of screening;
• Evidence of hepatic dysfunction ;
• Evidence of End-Stage Renal Disease;
• Females who are pregnant or lactating;
• Evidence or history of any significant physical or psychiatric condition including drug abuse, which, in the opinion of the Investigator, could jeopardize the safety of patients or affect their participation in the study. Additionally, the Investigator has the ability to exclude a patient if for any reason the Investigator judges the patient is not a good candidate for the study (e.g., illiteracy or poor understanding) or will not be able to follow study procedures;
• Participation in any investigational drug or device study or the use of any investigational drug or device within 30 days or five terminal phase half-lives of the drug whichever is longer, prior to the Screening Visit; or
• Previously enrolled in a clinical trial for Etripamil and received study drug during a perceived episode of PSVT;
• An immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.

Before randomization in this study, all patients will receive a test dose of an etripamil NS dosing regimen.