Clinical trial NCT04072835: Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia. NODE-303
Official title: The NODE-303 Study: Multi-Centre, Multi-National,Open Label, Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Paroxysmal Supraventricular Tachycardia
Keywords: PSVT
Lead sponsor: Milestone Pharmaceuticals Inc.
Sponsor class: OTHER
Collaborators: name: IQVIA Biotech
First posted: 2019-08-28
Enrollment: 1116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Adverse Events for Self-administered Etripamil NS Outside of the Clinical Setting.
timeFrame: From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months.
Secondary outcomes:
measure: Time to Conversion
timeFrame: Time to conversion up to 60 minutes after etripamil administration.
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: 1077
state: Arizona
city: Fremont
country: United States
facility: 1121
state: California
city: Stanford
country: United States
facility: 1035
state: California
city: Vista
country: United States
facility: 1023
state: California
city: West Hills
country: United States
facility: 1083
state: California
city: Littleton
country: United States
facility: 101
state: Colorado
city: Bridgeport
country: United States
facility: 1010
state: Connecticut
city: Trumbull
country: United States
facility: 1066
state: Connecticut
city: Bradenton
country: United States
facility: 1042
state: Florida
city: Daytona Beach
country: United States
facility: 1106
state: Florida
city: Edgewater
country: United States
facility: 1107
state: Florida
city: Hialeah
country: United States
facility: 1032
state: Florida
city: Miami
country: United States
facility: 1026
state: Florida
city: Miami
country: United States
facility: 1055
state: Florida
city: Naples
country: United States
facility: 1064
state: Florida
city: North Miami Beach
country: United States
facility: 1071
state: Florida
city: Orlando
country: United States
facility: 1009
state: Florida
city: Saint Augustine
country: United States
facility: 1060
state: Florida
city: Cumming
country: United States
facility: 1022
state: Georgia
city: Macon
country: United States
facility: 137
state: Georgia
city: Coeur d'Alene
country: United States
facility: 1115
state: Idaho
city: Peoria
country: United States
facility: 1045
state: Illinois
city: Fort Wayne
country: United States
facility: 149
state: Indiana
city: West Des Moines
country: United States
facility: 1025
state: Iowa
city: Monroe
country: United States
facility: 1008
state: Louisiana
city: Salisbury
country: United States
facility: 1007
state: Maryland
city: Boston
country: United States
facility: 1078
state: Massachusetts
city: Lansing
country: United States
facility: 166
state: Michigan
city: Rochester
country: United States
facility: 119
state: Minnesota
city: Saint Paul
country: United States
facility: 1093
state: Minnesota
city: Kansas City
country: United States
facility: 1099
state: Missouri
city: Elmer
country: United States
facility: 1134
state: New Jersey
city: Haddon Heights
country: United States
facility: 1133
state: New Jersey
city: New York
country: United States
facility: 114
state: New York
city: Southampton
country: United States
facility: 1021
state: New York
city: Charlotte
country: United States
facility: 129
state: North Carolina
city: Charlotte
country: United States
facility: 1065
state: North Carolina
city: Mount Airy
country: United States
facility: 1079
state: North Carolina
city: Statesville
country: United States
facility: 1018
state: North Carolina
city: Canton
country: United States
facility: 1024
state: Ohio
city: Cincinnati
country: United States
facility: 123
state: Ohio
city: Columbus
country: United States
facility: 142
state: Ohio
city: Oklahoma City
country: United States
facility: 1086
state: Oklahoma
city: Corvallis
country: United States
facility: 1123
state: Oregon
city: Hershey
country: United States
facility: 1031
state: Pennsylvania
city: Wyomissing
country: United States
facility: 1082
state: Pennsylvania
city: Yardley
country: United States
facility: 105
state: Pennsylvania
city: York
country: United States
facility: 1097
state: Pennsylvania
city: Rapid City
country: United States
facility: 122
state: South Dakota
city: Jackson
country: United States
facility: 1062
state: Tennessee
city: Memphis
country: United States
facility: 1012
state: Tennessee
city: Austin
country: United States
facility: 1047
state: Texas
city: Austin
country: United States
facility: 1092
state: Texas
city: Fort Worth
country: United States
facility: 1016
state: Texas
city: Houston
country: United States
facility: 1017
state: Texas
city: Plano
country: United States
facility: 1048
state: Texas
city: San Antonio
country: United States
facility: 1014
state: Texas
city: Riverton
country: United States
facility: 1004
state: Utah
city: Lynchburg
country: United States
facility: 117
state: Virginia
city: Richmond
country: United States
facility: 1076
state: Virginia
city: Richmond
country: United States
facility: 0116
state: Virginia
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: 5106
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: 5117
state: Buenos Aires
city: Mar Del Plata
country: Argentina
facility: 5112
state: Buenos Aires
city: Mar Del Plata
country: Argentina
facility: 5105
state: Buenos Aires
city: Quilmes
country: Argentina
facility: 5115
state: Buenos Aires
city: Ramos Mejía
country: Argentina
facility: 5122
state: Buenos Aires
city: San Nicolas
country: Argentina
facility: 5110
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: 5125
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: 5129
city: Corrientes
country: Argentina
facility: 5134
city: Córdoba
country: Argentina
facility: 5116
city: Córdoba
country: Argentina
facility: 5123
city: Córdoba
country: Argentina
facility: 5118
city: La Plata
country: Argentina
facility: 5102
city: Rosario
country: Argentina
facility: 5132
city: Salta
country: Argentina
facility: 5109
city: San Nicolas
country: Argentina
facility: 5130
city: Temperley
country: Argentina
facility: 5124
city: Belo Horizonte
country: Brazil
facility: 5221
state: Reg1
city: Brasília
country: Brazil
facility: 5217
state: Reg1
city: Campinas
country: Brazil
facility: 5215
state: Reg1
city: Canoas
country: Brazil
facility: 5222
state: Reg1
city: Curitiba
country: Brazil
facility: 5207
state: Reg1
city: Juiz de Fora
country: Brazil
facility: 5227
state: Reg1
city: Recife
country: Brazil
facility: 5209
state: Reg1
city: Salvador
country: Brazil
facility: 5214
state: Reg1
city: Santo André
country: Brazil
facility: 5219
state: Reg1
city: Sao Jose do Rio Preto
country: Brazil
facility: 5212
state: Reg1
city: São Paulo
country: Brazil
facility: 5220
state: Reg1
city: São Paulo
country: Brazil
facility: 5225
state: Reg1
city: Uberlândia
country: Brazil
facility: 5205
state: Reg1
city: Belo Horizonte
country: Brazil
facility: 5228
city: Campinas
country: Brazil
facility: 5202
city: Goiânia
country: Brazil
facility: 5201
city: Jaú
country: Brazil
facility: 5229
city: Rio De Janeiro
country: Brazil
facility: 5235
city: São Paulo
country: Brazil
facility: 5232
city: Tatuí
country: Brazil
facility: 5204
city: Votuporanga
country: Brazil
facility: 5231
city: Kelowna
country: Canada
facility: 2017
state: British Columbia
city: North Vancouver
country: Canada
facility: 2010
state: British Columbia
city: Saskatoon
country: Canada
facility: 2019
state: British Columbia
city: Surrey
country: Canada
facility: 2018
state: British Columbia
city: Vancouver
country: Canada
facility: 212
state: British Columbia
city: Victoria
country: Canada
facility: 213
state: British Columbia
city: Cambridge
country: Canada
facility: 215
state: Ontario
city: Hamilton
country: Canada
facility: 202
state: Ontario
city: Oshawa
country: Canada
facility: 2006
state: Ontario
city: Ottawa
country: Canada
facility: 2001
state: Ontario
city: Greenfield Park
country: Canada
facility: 2011
state: Quebec
city: Levis
country: Canada
facility: 2020
state: Quebec
city: Montreal
country: Canada
facility: 203
state: Quebec
city: Montréal
country: Canada
facility: 205
state: Quebec
city: Québec
country: Canada
facility: 2014
state: Quebec
city: Saint-Jerome
country: Canada
facility: 2003
state: Quebec
city: Sherbrooke
country: Canada
facility: 201
state: Quebec
city: St Jean sur Richelieu
country: Canada
facility: 2002
state: Quebec
city: Armenia
country: Colombia
facility: 5409
city: Barranquilla
country: Colombia
facility: 5404
city: Bucaramanga
country: Colombia
facility: 5408
city: Medellín
country: Colombia
facility: 5401
city: Punta de Cartagena
country: Colombia
facility: 5407
city: San Gil
country: Colombia
facility: 5403
Study officials:
affiliation: Milestone Pharmaceuticals
name: Francis Plat, MD
role: STUDY_DIRECTOR
References: