Topline results were announced from the phase 3 NODE-301 trial of etripamil nasal spray (Milestone Pharmaceuticals), a novel short-acting calcium channel blocker, being investigated for the at-home treatment of acute paroxysmal supraventricular tachycardia (PSVT).
The multicenter, double-blind, placebo-controlled trial enrolled 431 patients to assess the efficacy and safety of etripamil for terminating episodes of PSVT in an outpatient setting. Following an in-office test dose of etripamil, patients were randomized 2:1 to receive etripamil 70mg or placebo. At the onset of PSVT symptoms, patients applied a wireless cardiac monitor to their chest to record heart rhythm, performed a vagal maneuver, and administered etripamil if symptoms persisted.
The primary end point was time to conversion of an SVT episode to sinus rhythm after the administration of etripamil. Secondary outcomes included the relief of symptoms commonly associated with an episode of SVT, such as rapid pulse, heart palpitations, anxiety, shortness of breath and dizziness, as well as satisfaction with treatment based on ratings from the Treatment Satisfaction Questionnaire for Medication (TSQM-9).
Results showed that etripamil did not meet the primary end point over the 5-hour period following study drug administration (median time to conversion of 25 minutes [95% CI, 16-43] after etripamil administration compared with 50 minutes [95% CI, 31-101] for placebo; P =.12). Etripamil was associated with rapid conversion during the first 45 minutes after treatment (P =.02), however, the Company stated the results from the latter part of the analysis confounded the statistical analysis of the primary end point.
In addition, etripamil demonstrated statistically significant improvements for treatment satisfaction vs placebo, as measured by TSQM-9, including global satisfaction (P =.0069) and effectiveness scores (P =.0015).
Regarding safety, the most common treatment-emergent adverse reactions included nasal irritation and congestion. Reactions were characterized as being mild in severity by patients and transient in nature. No significant differences were observed for severe reactions between etripamil and placebo.
“NODE-301 is a first-of-its-kind study, and as such encountered a number of challenges relative to studying SVT episodes outside of a controlled electrophysiology laboratory environment,” said Bruce Stambler, MD, FHRS, Piedmont Heart Institute, Atlanta, GA. “The safety results support at-home use and the multiple efficacy signals show us that, with a confirmatory study, etripamil could fulfill the promise of delivering a fast-acting, patient administered therapy for PSVT.”
The Company is currently investigating etripamil for the treatment of PSVT patients in the ongoing NODE-301B, NODE-302, and NODE-303 studies. The Company plans to request a meeting with regulators to discuss NODE-301 findings and ongoing studies.
For more information visit milestonepharma.com.