Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia. NODE-303
- Registration Number
- NCT04072835
- Lead Sponsor
- Milestone Pharmaceuticals Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1116
A participant was eligible for study participation if they met all of the following criteria:
- 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.
- Was at least 18 years of age;
- Signed NODE-303 written informed consent
- 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.
- Willing and able to comply with study procedures
A participant was excluded from the study if they met any of the following criteria:
-
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.
-
History of allergic reaction to verapamil
-
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.
-
History or evidence of ventricular pre-excitation, e.g., delta waves, Wolff- Parkinson-White syndrome
-
History or evidence of a second- or third-degree AV block
-
History or evidence of severe ventricular arrhythmia (e.g., torsades de pointes, ventricular fibrillation, or sustained ventricular tachycardia).
-
Symptoms of congestive heart failure New York Heart Association Class II to IV
-
SBP < 90 mmHg at Screening, Baseline or any Follow-up Visit.
-
Severe symptoms of hypotension experienced during PSVT episodes.
-
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
-
History of syncope due to an arrhythmic etiology at any time, or history in last 5 years of unexplained syncope
-
Was pregnant or breastfeeding
-
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.
-
History of Acute Coronary Syndrome (ACS) or stroke within 6 months of screening
-
Evidence of renal dysfunction as determined by an estimated glomerular filtration rate assessed at the Screening Visit as follows:
- <60mL/min/1.73m2 for participants <60 years of age;
- <40mL/min/1.73m2 for participants ≥60 and <70 years of age
- <35mL/min/1.73m2 for participants ≥70 years of age
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Etripamil NS 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
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events for Self-administered Etripamil NS Outside of the Clinical Setting. From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Number of participants with any adverse events experienced from baseline up to the final study visit including the treatment of up to 4 perceived PSVT episodes.
- Secondary Outcome Measures
Name Time Method Time to Conversion Time to conversion up to 60 minutes after etripamil administration. Kaplan-Meier estimates of time to conversion up to 60 minutes after etripamil administration for adjudicated conversion of confirmed episodes of PSVT to SR (Sinus Rhythm) reported at Follow-up Visit 1.
Trial Locations
- Locations (124)
1123
🇺🇸Corvallis, Oregon, United States
105
🇺🇸Yardley, Pennsylvania, United States
1035
🇺🇸Stanford, California, United States
1023
🇺🇸Vista, California, United States
5231
🇧🇷Votuporanga, Brazil
1026
🇺🇸Miami, Florida, United States
1055
🇺🇸Miami, Florida, United States
1078
🇺🇸Boston, Massachusetts, United States
142
🇺🇸Columbus, Ohio, United States
1017
🇺🇸Houston, Texas, United States
123
🇺🇸Cincinnati, Ohio, United States
1014
🇺🇸San Antonio, Texas, United States
5134
🇦🇷Corrientes, Argentina
2003
🇨🇦Saint-Jerome, Quebec, Canada
1012
🇺🇸Memphis, Tennessee, United States
1062
🇺🇸Jackson, Tennessee, United States
1133
🇺🇸Haddon Heights, New Jersey, United States
1010
🇺🇸Bridgeport, Connecticut, United States
1066
🇺🇸Trumbull, Connecticut, United States
5122
🇦🇷Ramos Mejía, Buenos Aires, Argentina
5125
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
5129
🇦🇷Ciudad Autónoma de Buenos Aires, Argentina
5116
🇦🇷Córdoba, Argentina
5109
🇦🇷Salta, Argentina
5117
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
5130
🇦🇷San Nicolas, Argentina
2011
🇨🇦Greenfield Park, Quebec, Canada
2002
🇨🇦St Jean sur Richelieu, Quebec, Canada
5404
🇨🇴Barranquilla, Colombia
5407
🇨🇴Punta de Cartagena, Colombia
212
🇨🇦Vancouver, British Columbia, Canada
1008
🇺🇸Monroe, Louisiana, United States
2010
🇨🇦North Vancouver, British Columbia, Canada
1077
🇺🇸Gilbert, Arizona, United States
5106
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
2019
🇨🇦Saskatoon, British Columbia, Canada
1115
🇺🇸Coeur d'Alene, Idaho, United States
1134
🇺🇸Elmer, New Jersey, United States
122
🇺🇸Rapid City, South Dakota, United States
5112
🇦🇷Mar Del Plata, Buenos Aires, Argentina
5123
🇦🇷Córdoba, Argentina
5105
🇦🇷Mar Del Plata, Buenos Aires, Argentina
5115
🇦🇷Quilmes, Buenos Aires, Argentina
5110
🇦🇷San Nicolas, Buenos Aires, Argentina
5132
🇦🇷Rosario, Argentina
5118
🇦🇷Córdoba, Argentina
5102
🇦🇷La Plata, Argentina
5403
🇨🇴San Gil, Colombia
2018
🇨🇦Surrey, British Columbia, Canada
203
🇨🇦Montreal, Quebec, Canada
213
🇨🇦Victoria, British Columbia, Canada
1009
🇺🇸Orlando, Florida, United States
1047
🇺🇸Austin, Texas, United States
1092
🇺🇸Austin, Texas, United States
1121
🇺🇸Fremont, California, United States
1083
🇺🇸West Hills, California, United States
101
🇺🇸Littleton, Colorado, United States
1042
🇺🇸Bradenton, Florida, United States
1106
🇺🇸Daytona Beach, Florida, United States
1107
🇺🇸Edgewater, Florida, United States
1032
🇺🇸Hialeah, Florida, United States
1064
🇺🇸Naples, Florida, United States
1071
🇺🇸North Miami Beach, Florida, United States
1060
🇺🇸Saint Augustine, Florida, United States
1022
🇺🇸Cumming, Georgia, United States
137
🇺🇸Macon, Georgia, United States
1045
🇺🇸Peoria, Illinois, United States
149
🇺🇸Fort Wayne, Indiana, United States
1025
🇺🇸West Des Moines, Iowa, United States
1007
🇺🇸Salisbury, Maryland, United States
166
🇺🇸Lansing, Michigan, United States
1093
🇺🇸Saint Paul, Minnesota, United States
1021
🇺🇸Southampton, New York, United States
129
🇺🇸Charlotte, North Carolina, United States
1079
🇺🇸Mount Airy, North Carolina, United States
114
🇺🇸New York, New York, United States
1065
🇺🇸Charlotte, North Carolina, United States
1018
🇺🇸Statesville, North Carolina, United States
1024
🇺🇸Canton, Ohio, United States
1031
🇺🇸Hershey, Pennsylvania, United States
1097
🇺🇸York, Pennsylvania, United States
1082
🇺🇸Wyomissing, Pennsylvania, United States
1004
🇺🇸Riverton, Utah, United States
1016
🇺🇸Fort Worth, Texas, United States
1048
🇺🇸Plano, Texas, United States
117
🇺🇸Lynchburg, Virginia, United States
5124
🇦🇷Temperley, Argentina
5221
🇧🇷Belo Horizonte, Reg1, Brazil
5217
🇧🇷Brasília, Reg1, Brazil
5215
🇧🇷Campinas, Reg1, Brazil
5222
🇧🇷Canoas, Reg1, Brazil
5227
🇧🇷Juiz de Fora, Reg1, Brazil
5207
🇧🇷Curitiba, Reg1, Brazil
5209
🇧🇷Recife, Reg1, Brazil
5219
🇧🇷Santo André, Reg1, Brazil
5214
🇧🇷Salvador, Reg1, Brazil
5212
🇧🇷Sao Jose do Rio Preto, Reg1, Brazil
5220
🇧🇷São Paulo, Reg1, Brazil
5225
🇧🇷São Paulo, Reg1, Brazil
5205
🇧🇷Uberlândia, Reg1, Brazil
5229
🇧🇷Jaú, Brazil
5202
🇧🇷Campinas, Brazil
5235
🇧🇷Rio De Janeiro, Brazil
5228
🇧🇷Belo Horizonte, Brazil
5201
🇧🇷Goiânia, Brazil
5232
🇧🇷São Paulo, Brazil
5204
🇧🇷Tatuí, Brazil
2017
🇨🇦Kelowna, British Columbia, Canada
215
🇨🇦Cambridge, Ontario, Canada
202
🇨🇦Hamilton, Ontario, Canada
2001
🇨🇦Ottawa, Ontario, Canada
2020
🇨🇦Levis, Quebec, Canada
205
🇨🇦Montréal, Quebec, Canada
2014
🇨🇦Québec, Quebec, Canada
201
🇨🇦Sherbrooke, Quebec, Canada
5409
🇨🇴Armenia, Colombia
5408
🇨🇴Bucaramanga, Colombia
5401
🇨🇴Medellín, Colombia
119
🇺🇸Rochester, Minnesota, United States
1099
🇺🇸Kansas City, Missouri, United States
1086
🇺🇸Oklahoma City, Oklahoma, United States
1076
🇺🇸Richmond, Virginia, United States
0116
🇺🇸Richmond, Virginia, United States
2006
🇨🇦Oshawa, Ontario, Canada