NCT03464019

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

Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Efficacy, and Safety Study of Etripamil Nasal Spray for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia. NODE 301 and RAPID Studies

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,097 (actual)
• Sponsor: Milestone Pharmaceuticals Inc. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a three-part, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil nasal spray (NS) self-administered by participants who experienced an episode of paroxysmal supraventricular tachycardia (PSVT) in an at-home setting. 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. Part 2 (also referred as the RAPID study) included participants that did not receive the randomized study drug in Part 1 and newly enrolled participants until the 180th positively adjudicated PSVT episode in Part 2. 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).

Detailed description

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. NODE-301 study comprised 6 arms: * 2 arms consisting of participants enrolled in Part 1 that treated a perceived episode of PSVT with randomized study drug (etripamil NS 70 mg or placebo) in a 2:1 ratio. * 1 arm consisting of participants that only received the Test Dose in Part 1. * 2 arms consisting of participants enrolled in Parts 2 and 3 that treated a perceived episode of PSVT with randomized study drug (etripamil NS 70 mg with optional second dose of 70 mg etripamil or placebo) in a 1:1 ratio and could be enrolled in the open-label period to treat an additional PSVT episode with etripamil * 1 arm consisting of participants that only received the Test Dose in Parts 2 and 3.

Conditions

• Paroxysmal Supraventricular Tachycardia

Interventions

Type	Name	Description
DRUG	Etripamil	Etripamil administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.
DRUG	Placebo	Placebo administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.
DRUG	Etripamil Test Dose	During the Test Dose, etripamil administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.

Timeline

• Start date: 2018-06-18
• Primary completion: 2023-01-20
• Completion: 2023-01-20
• First posted: 2018-03-13
• Last updated: 2024-07-12
• Results posted: 2024-07-12

Locations

161 sites across 9 countries: United States, Belgium, Canada, France, Germany, Hungary, Netherlands, Poland, Spain

Regulatory

• FDA-regulated drug study