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

NCT ID: NCT04072835

Last Updated: 2024-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-23
• Study Completion Date: 2023-01-26

Brief Summary

NODE-303 was a multi-center, open label study to evaluate the safety of etripamil NS in participants with Paroxysmal Supraventricular Tachycardia (PSVT). Participants were provided with an ambulatory Cardiac Monitoring System (CMS) to help document PSVT episodes. The CMS was self-applied by the participant, when they felt the onset of PSVT symptoms. Participants self-administered etripamil NS if vagal maneuver was ineffective. After an episode of PSVT where study drug was administered, the participant returned to the investigative site and had the option to continue in NODE-303 and manage up to three subsequent episodes of PSVT with etripamil NS for a maximum of four episodes.

Detailed Description

NODE-303 was a multi-center, open label study to evaluate the safety of etripamil NS in participants with PSVT. Participants were provided with an ambulatory CMS to help document PSVT episodes. The CMS was self-applied by the participant, when they felt the onset of PSVT symptoms. Participants self-administered etripamil NS 70 mg if vagal maneuver (VM) was ineffective. Approximately 2 years after study initiation, a protocol amendment was implemented to allow participants to administer a second dose of etripamil 70 mg 10 minutes after the first dose, if PSVT symptoms persisted. After an episode of PSVT where study drug was administered, the participant returned to the investigative site and had the option to continue in NODE-303 and manage up to three subsequent episodes of PSVT with etripamil NS for a maximum of four episodes.

The study included:

A Screening Visit during which the Investigator verified that the participant met the eligibility criteria of the NODE-303 study, obtained the signed informed consent, took blood and urine for laboratory evaluations, and conducted other screening procedures. The informed consent for NODE-303 was applicable for the initial and all subsequent PSVT episodes. A Baseline Visit during which the site confirmed eligibility, concomitant medications, trained the participant on study procedures, and gave the participant study drug, participant reported outcome (PRO) materials, and the CMS materials. A Treatment Period during which the participant completed the monthly PRO survey, self-identified symptoms of PSVT, used the CMS during 60 minutes, performed a VM, and self-administered etripamil NS if the symptoms did not resolve after the VM. Participants could be contacted during this period for reminders and training on what to do during a PSVT episode. Participants also completed a per episode survey after any PSVT episode they experience. During the Treatment Period, Follow-up Visits occurred at the study site up to 14 days after each episode of PSVT treated with etripamil NS, and during which the Investigator evaluated the results of the last usage of etripamil NS and reassessed participant's eligibility to continue in the study based on study inclusion and exclusion criteria. Participants who were eligible to continue in the study received additional study medication.

A Final Study Visit occurred when a participant discontinued or withdrew from the study, or when the overall study was completed, or the participant had completed the maximum number of doses. NODE-303 continued until enough documented self-administrations of etripamil NS were 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 depended on the rate of accrual of the primary endpoint, unique participants with an episode. When the criteria for concluding the study were met, the Sponsor announced the CSED for the entire study and sites were informed in advance to schedule all final participant visits prior to the CSED.

Conditions

Paroxysmal Supraventricular Tachycardia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Etripamil NS

Participants self-administered etripamil NS 70 mg. After implementation of protocol amendment 2.1 (16 March 2021), participants had the option to administer a second dose of etripamil 70 mg 10 minutes after the first dose, if PSVT symptoms persisted

Group Type: EXPERIMENTAL

Etripamil NS

Intervention Type: DRUG

Participants were provided with an ambulatory Cardiac Monitoring System (CMS) to help document PSVT episodes. The CMS was self-applied by the participant, when PSVT symptoms begin. Participants self-administered etripamil NS if vagal maneuver was ineffective. After implementation of protocol amendment 2.1, participants had the option to administer a second dose of etripamil 70 mg 10 minutes after the first dose, if symptoms persisted. After an episode of PSVT where drug was administered, the participant returned to the investigative site for a study visit and was given the option to continue in NODE-303 and manage up to three subsequent episodes of PSVT with etripamil NS for a maximum of four episodes.

Not Treated

Participants not treated with etripamil NS for a PSVT episode.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Etripamil NS

Participants were provided with an ambulatory Cardiac Monitoring System (CMS) to help document PSVT episodes. The CMS was self-applied by the participant, when PSVT symptoms begin. Participants self-administered etripamil NS if vagal maneuver was ineffective. After implementation of protocol amendment 2.1, participants had the option to administer a second dose of etripamil 70 mg 10 minutes after the first dose, if symptoms persisted. After an episode of PSVT where drug was administered, the participant returned to the investigative site for a study visit and was given the option to continue in NODE-303 and manage up to three subsequent episodes of PSVT with etripamil NS for a maximum of four episodes.

Intervention Type: DRUG

Other Intervention Names

MSP-2017

Eligibility Criteria

Inclusion Criteria

A participant was eligible for study participation if they met all of the following criteria:

1. Had been diagnosed with PSVT by a medical professional, and reported having at least one previous episode of PSVT. For clarity, PSVT referred to episodic Supraventricular Tachycardia (SVT) that included the atrioventricular (AV) node as a critical part of reentrant circuit.

2. Was at least 18 years of age;

3. Signed NODE-303 written informed consent

4. Women of childbearing potential had to be willing to use at least 1 form of contraception during the trial, and had to be willing to discontinue from the study should they have become or planned to become pregnant. Postmenopausal females were defined as having amenorrhea for at least 12 months prior to Screening without an alternative medical cause.

5. Willing and able to comply with study procedures

Exclusion Criteria

A participant was excluded from the study if they met any of the following criteria:

1. Participants with only a history of atrial arrhythmia that did not involve the atrioventricular (AV) node as part of the tachycardia circuit (e.g. atrial fibrillation, atrial flutter, intra-atrial tachycardia) were not eligible. Participants with a history of these tachycardias who were also diagnosed with PSVT were eligible.

2. History of allergic reaction to verapamil

3. Current therapy with digoxin, or any Class I or III antiarrhythmic drug. Participants could be eligible if these drugs were stopped at least five half-lives before the administration of etripamil NS. The only exception was amiodarone which had to be stopped 30 days before enrollment.

4. History or evidence of ventricular pre-excitation, e.g., delta waves, Wolff- Parkinson-White syndrome

5. History or evidence of a second- or third-degree AV block

6. History or evidence of severe ventricular arrhythmia (e.g., torsades de pointes, ventricular fibrillation, or sustained ventricular tachycardia).

7. Symptoms of congestive heart failure New York Heart Association Class II to IV

8. SBP < 90 mmHg at Screening, Baseline or any Follow-up Visit.

9. Severe symptoms of hypotension experienced during PSVT episodes.

10. Significant physical or psychiatric condition including alcoholism or drug abuse, which, in the opinion of the Investigator, could jeopardize the safety of the participant, or impede the participant's capacity to follow the study procedures

11. History of syncope due to an arrhythmic etiology at any time, or history in last 5 years of unexplained syncope

12. Was pregnant or breastfeeding

13. 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.

14. History of Acute Coronary Syndrome (ACS) or stroke within 6 months of screening

15. Evidence of renal dysfunction as determined by an estimated glomerular filtration rate assessed at the Screening Visit as follows:

1. <60mL/min/1.73m2 for participants <60 years of age;

2. <40mL/min/1.73m2 for participants ≥60 and <70 years of age

3. <35mL/min/1.73m2 for participants ≥70 years of age

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IQVIA Biotech

INDUSTRY

Sponsor Role: collaborator

Milestone Pharmaceuticals Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francis Plat, MD

Role: STUDY_DIRECTOR

Milestone Pharmaceuticals

Locations

1077

Gilbert, Arizona, United States

1121

Fremont, California, United States

1035

Stanford, California, United States

1023

Vista, California, United States

1083

West Hills, California, United States

101

Littleton, Colorado, United States

1010

Bridgeport, Connecticut, United States

1066

Trumbull, Connecticut, United States

1042

Bradenton, Florida, United States

1106

Daytona Beach, Florida, United States

1107

Edgewater, Florida, United States

1032

Hialeah, Florida, United States

1026

Miami, Florida, United States

1055

Miami, Florida, United States

1064

Naples, Florida, United States

1071

North Miami Beach, Florida, United States

1009

Orlando, Florida, United States

1060

Saint Augustine, Florida, United States

1022

Cumming, Georgia, United States

137

Macon, Georgia, United States

1115

Coeur d'Alene, Idaho, United States

1045

Peoria, Illinois, United States

149

Fort Wayne, Indiana, United States

1025

West Des Moines, Iowa, United States

1008

Monroe, Louisiana, United States

1007

Salisbury, Maryland, United States

1078

Boston, Massachusetts, United States

166

Lansing, Michigan, United States

119

Rochester, Minnesota, United States

1093

Saint Paul, Minnesota, United States

1099

Kansas City, Missouri, United States

1134

Elmer, New Jersey, United States

1133

Haddon Heights, New Jersey, United States

114

New York, New York, United States

1021

Southampton, New York, United States

129

Charlotte, North Carolina, United States

1065

Charlotte, North Carolina, United States

1079

Mount Airy, North Carolina, United States

1018

Statesville, North Carolina, United States

1024

Canton, Ohio, United States

123

Cincinnati, Ohio, United States

142

Columbus, Ohio, United States

1086

Oklahoma City, Oklahoma, United States

1123

Corvallis, Oregon, United States

1031

Hershey, Pennsylvania, United States

1082

Wyomissing, Pennsylvania, United States

105

Yardley, Pennsylvania, United States

1097

York, Pennsylvania, United States

122

Rapid City, South Dakota, United States

1062

Jackson, Tennessee, United States

1012

Memphis, Tennessee, United States

1047

Austin, Texas, United States

1092

Austin, Texas, United States

1016

Fort Worth, Texas, United States

1017

Houston, Texas, United States

1048

Plano, Texas, United States

1014

San Antonio, Texas, United States

1004

Riverton, Utah, United States

117

Lynchburg, Virginia, United States

1076

Richmond, Virginia, United States

0116

Richmond, Virginia, United States

5106

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

5117

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

5112

Mar del Plata, Buenos Aires, Argentina

5105

Mar del Plata, Buenos Aires, Argentina

5115

Quilmes, Buenos Aires, Argentina

5122

Ramos Mejía, Buenos Aires, Argentina

5110

San Nicolás de los Arroyos, Buenos Aires, Argentina

5129

Buenos Aires, , Argentina

5125

Buenos Aires, , Argentina

5134

Corrientes, , Argentina

5116

Córdoba, , Argentina

5123

Córdoba, , Argentina

5118

Córdoba, , Argentina

5102

La Plata, , Argentina

5132

Rosario, , Argentina

5109

Salta, , Argentina

5130

San Nicolás, , Argentina

5124

Temperley, , Argentina

5221

Belo Horizonte, REG1, Brazil

5217

Brasília, REG1, Brazil

5215

Campinas, REG1, Brazil

5222

Canoas, REG1, Brazil

5207

Curitiba, REG1, Brazil

5227

Juiz de Fora, REG1, Brazil

5209

Recife, REG1, Brazil

5214

Salvador, REG1, Brazil

5219

Santo André, REG1, Brazil

5212

São José do Rio Preto, REG1, Brazil

5220

São Paulo, REG1, Brazil

5225

São Paulo, REG1, Brazil

5205

Uberlândia, REG1, Brazil

5228

Belo Horizonte, , Brazil

5202

Campinas, , Brazil

5201

Goiânia, , Brazil

5229

Jaú, , Brazil

5235

Rio de Janeiro, , Brazil

5232

São Paulo, , Brazil

5204

Tatuí, , Brazil

5231

Votuporanga, , Brazil

2017

Kelowna, British Columbia, Canada

2010

North Vancouver, British Columbia, Canada

2019

Saskatoon, British Columbia, Canada

2018

Surrey, British Columbia, Canada

212

Vancouver, British Columbia, Canada

213

Victoria, British Columbia, Canada

215

Cambridge, Ontario, Canada

202

Hamilton, Ontario, Canada

2006

Oshawa, Ontario, Canada

2001

Ottawa, Ontario, Canada

2011

Greenfield Park, Quebec, Canada

2020

Lévis, Quebec, Canada

205

Montreal, Quebec, Canada

203

Montreal, Quebec, Canada

2014

Québec, Quebec, Canada

2002

Saint-Jean-sur-Richelieu, Quebec, Canada

2003

Saint-Jérôme, Quebec, Canada

201

Sherbrooke, Quebec, Canada

5409

Armenia, , Colombia

5404

Barranquilla, , Colombia

5408

Bucaramanga, , Colombia

5401

Medellín, , Colombia

5407

Punta de Cartagena, , Colombia

5403

San Gil, , Colombia

Countries

United States; Argentina; Brazil; Canada; Colombia

References

Ip JE, Coutu B, Ip JH, Noseworthy PA, Parody ML, Rafii F, Sears SF, Singh N, Stambler BS, Tahirkheli NK, Agudelo-Uribe J, Hu D, Shardonofsky S, Sheikh MB, Holz A, Bharucha DB, Camm AJ. Etripamil Nasal Spray for Recurrent Paroxysmal Supraventricular Tachycardia Conversion: Results From the NODE-303 Open-Label Study. J Cardiovasc Electrophysiol. 2025 Sep 11. doi: 10.1111/jce.70086. Online ahead of print.

Reference Type: DERIVED

PMID: 40931676 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

NODE-303

Identifier Type: -

Identifier Source: org_study_id