Efficacy and Safety of Etripamil for the Termination of Spontaneous Paroxysmal Supraventricular Tachycardia (PSVT).

NODE-301 was a three-part, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil NS self-administered by participants who experienced an episode of PSVT in an at-home setting. Each episode was documented by an ambulatory Cardiac Monitoring System (CMS) that was placed on the chest by the participants or caregiver when symptoms begin and recorded at least 5 hours of continuous electrocardiogram (ECG).

This was an event-driven study. The study comprised of three parts: Parts 1, 2, and 3.

NODE-301 Part 1 included participants that received the randomized study drug to treat an episode of PSVT until the 150th positively adjudicated PSVT episode (January 15th, 2020). Participants were randomized to etripamil 70 mg or placebo in a 2:1 ratio. Participants had a Test Dose Randomization Visit where they received 70 mg etripamil in sinus rhythm and a Treatment Period during which they could administer the randomized study drug during a perceived episode of PSVT.

Part 2 (also referred as the RAPID study) included participants that did not use the randomized study drug to treat a perceived episode of PSVT before the Part 1 data cutoff and newly enrolled participants. Before randomization in the RAPID study, all participants received a Test Dose of etripamil consisting of an initial dose of etripamil 70 mg followed by a second dose of etripamil 70 mg 10 minutes later to evaluate tolerability and to train participants on the study procedures. After a successful Test Dose, participants in Part 2 were randomized to etripamil or placebo in a 1:1 ratio. When experiencing a PSVT episode, participants were instructed to administer a first dose of randomized study drug (70 mg etripamil or placebo) followed 10 minutes later, if PSVT symptoms persisted, by a second dose of study drug (70 mg etripamil or placebo). After having administered the randomized study drug for a perceived episode of PSVT, participants could enter an open-label period during which they had the possibility to treat a second episode of PSVT with open-label etripamil (70 mg etripamil with optional second dose of 70 mg etripamil).

Part 2 continued until the 180th positively adjudicated PSVT episode (the data on which the primary efficacy analysis of RAPID was conducted) (July 20th 2022). The study continued for approximately 6 months after the 180th positively adjudicated PSVT episode in Part 2 and this extension is referred to as Part 3 (also referred to as RAPID Extension). The design of Parts 2 and 3 were the same and therefore their results are combined in this publication.