Trial Outcomes & Findings for Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia. NODE-303 (NCT NCT04072835)

Last Updated: 2024-05-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1116 participants

Primary outcome 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.

Results posted on

2024-05-23

Participant Flow

To enroll participants in the study, a diagnosis of PSVT by a medical professional and history of at least one previous episode of PSVT were required. The first participant was enrolled on September 23, 2019 and the last participant was enrolled on October 27, 2022.

Participants had to meet all inclusion criteria and none of the exclusion criteria to be enrolled in the study. At baseline, the participants received the CMS, the study drug, and instructions on what to do when they started to feel the symptoms of PSVT.

Participant milestones

Participant milestones
Measure	All Participants Participants self-administered etripamil NS 70 mg and after the implementation of protocol amendment 2.1, the participants had the option to administer a second dose of etripamil 70 mg 10 minutes later, if PSVT symptoms persisted. Considering this is an event-driven study, not all participants experienced a PSVT and could administered the study drug before the study was completed. This arm includes all participants that were enrolled in the study.
Overall Study STARTED	1116
Overall Study Participants Who Completed the Study With at Least 1 Treated Perceived PSVT Episode	503
Overall Study Participants Who Treated 1 Perceived PSVT Episode in the Study	220
Overall Study Participants Who Treated 2 Perceived PSVT Episodes in the Study	118
Overall Study Participants Who Treated 3 Perceived PSVT Episodes in the Study	62
Overall Study Participants Who Treated 4 Perceived PSVT Episodes in the Study	103
Overall Study COMPLETED	103
Overall Study NOT COMPLETED	1013

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants Participants self-administered etripamil NS 70 mg and after the implementation of protocol amendment 2.1, the participants had the option to administer a second dose of etripamil 70 mg 10 minutes later, if PSVT symptoms persisted. Considering this is an event-driven study, not all participants experienced a PSVT and could administered the study drug before the study was completed. This arm includes all participants that were enrolled in the study.
Overall Study Overall trial ended	603
Overall Study Ablation	97
Overall Study Withdrawal of consent	66
Overall Study Physician Decision	50
Overall Study Lost to Follow-up	39
Overall Study Participant no longer meets the inclusion/exclusion criteria	38
Overall Study Participant wanted to try other therapy or treatment	34
Overall Study Adverse Event	25
Overall Study Participant non-compliance / Protocol violation(s)	25
Overall Study Death	11
Overall Study Participant felt the drug did not work	8
Overall Study Participant tolerability	5
Overall Study Missing	5
Overall Study Participant withdrawn due to COVID-19 situation	4
Overall Study Pregnancy	3

Baseline Characteristics

Not all participants reported the age at first diagnostic of PSVT

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=1116 Participants Participants self-administered etripamil NS 70 mg and after the implementation of protocol amendment 2.1, the participants had the option to administer a second dose of etripamil 70 mg 10 minutes later, if PSVT symptoms persisted. Considering this is an event-driven study, not all participants experienced a PSVT and could administered the study drug before the study was completed. This arm/group includes all participants that were enrolled in the study.
Age, Continuous Age at informed consent signed	54.3 years STANDARD_DEVIATION 14.0 • n=1116 Participants
Age, Continuous Age at first diagnosis of PSVT	48.3 years STANDARD_DEVIATION 16.2 • n=875 Participants • Not all participants reported the age at first diagnostic of PSVT
Age, Customized Age at informed consent signed · 18 to < 60 years	695 Participants n=1116 Participants
Age, Customized Age at informed consent signed · 60 to < 70 years	263 Participants n=1116 Participants
Age, Customized Age at informed consent signed · ≥ 70 years	158 Participants n=1116 Participants
Sex: Female, Male Female	762 Participants n=1116 Participants
Sex: Female, Male Male	354 Participants n=1116 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	396 Participants n=1116 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	696 Participants n=1116 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	24 Participants n=1116 Participants
Race (NIH/OMB) American Indian or Alaska Native	8 Participants n=1116 Participants
Race (NIH/OMB) Asian	30 Participants n=1116 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=1116 Participants
Race (NIH/OMB) Black or African American	57 Participants n=1116 Participants
Race (NIH/OMB) White	913 Participants n=1116 Participants
Race (NIH/OMB) More than one race	0 Participants n=1116 Participants
Race (NIH/OMB) Unknown or Not Reported	106 Participants n=1116 Participants
Weight	82.3 Kg STANDARD_DEVIATION 21.5 • n=1116 Participants
Height	167.2 cm STANDARD_DEVIATION 9.4 • n=1111 Participants • Not all participants reported the height
Time since first PSVT diagnosis	6.2 years STANDARD_DEVIATION 8.9 • n=875 Participants • Not all participants reported the time since first PSVT diagnosis
Number of participant-reported PSVT episodes in the past year	8.6 episodes STANDARD_DEVIATION 16.5 • n=1064 Participants • Not all participants reported PSVT episodes in the past year
Number of participant-reported emergency department visits since diagnosis	3.5 emergency department visits STANDARD_DEVIATION 6.3 • n=647 Participants • Not all participants reported emergency department visit
Number of participant-reported urgent care visits since diagnosis	5.0 urgent care visits STANDARD_DEVIATION 11.2 • n=168 Participants • Not all participants reported urgent care visits
Number of participant-reported visits to doctor's office since diagnosis	5.0 visits to doctor's office STANDARD_DEVIATION 10.2 • n=324 Participants • Not all participants reported visits to doctor's office
Number of participant-reported visits to the arrhythmia clinic / day hospital since diagnosis	5.0 visits to the arrhythmia clinic/day hosp STANDARD_DEVIATION 13.6 • n=61 Participants • Not all participants reported visits to the arrhythmia clinic/day hospital

PRIMARY outcome

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.

Population: The Safety Population includes all participants who self-administered any amount of study drug.

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.

Outcome measures

Outcome measures
Measure	Etripamil n=503 Participants Participants self-administered etripamil NS 70 mg and after the implementation of protocol amendment 2.1, the participants had the option to administer a second dose of etripamil 70 mg 10 minutes later, if PSVT symptoms persisted. Only participants that received etripamil are included in this group. All adverse events reactions were included regardless of treatment-emergent status and causality assessment
Number of Participants With Adverse Events for Self-administered Etripamil NS Outside of the Clinical Setting.	324 Participants

SECONDARY outcome

Timeframe: Time to conversion up to 60 minutes after etripamil administration.

Population: The Efficacy Population includes participants who received study drug for an event confirmed as PSVT by the Sponsor's medical review of the ECG CMS data.

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.

Outcome measures

Outcome measures
Measure	Etripamil n=231 Participants Participants self-administered etripamil NS 70 mg and after the implementation of protocol amendment 2.1, the participants had the option to administer a second dose of etripamil 70 mg 10 minutes later, if PSVT symptoms persisted. Only participants that received etripamil are included in this group. All adverse events reactions were included regardless of treatment-emergent status and causality assessment
Time to Conversion	17.7 minutes Interval 13.9 to 26.2

Adverse Events

Etripamil

Serious events: 34 serious events

Other events: 237 other events

Deaths: 4 deaths

Not Treated

Serious events: 22 serious events

Other events: 32 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Etripamil n=503 participants at risk Participants self-administered etripamil NS 70 mg and after the implementation of protocol amendment 2.1, the participants had the option to administer a second dose of etripamil 70 mg 10 minutes later, if PSVT symptoms persisted.	Not Treated n=613 participants at risk Participants not treated with etripamil NS. Participants were still waiting for their first perceived PSVT episode when this event-driven study was ended by the sponsor.
Nervous system disorders Headache	5.6% 28/503 • Number of events 40 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column	0.65% 4/613 • Number of events 5 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column
Respiratory, thoracic and mediastinal disorders Nasal discomfort	30.4% 153/503 • Number of events 235 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column	0.00% 0/613 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.3% 72/503 • Number of events 96 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column	0.16% 1/613 • Number of events 1 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	13.5% 68/503 • Number of events 98 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column	0.16% 1/613 • Number of events 1 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column
Respiratory, thoracic and mediastinal disorders Epistaxis	8.2% 41/503 • Number of events 49 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column	0.00% 0/613 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column
Infections and infestations Corona virus infection	5.6% 28/503 • Number of events 30 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column	4.2% 26/613 • Number of events 28 • From Baseline until a maximum of 4 episodes of perceived PSVT are treated with study drug, up to a maximum duration of 40 months. Adverse Events (including All-Cause Mortality, Serious Adverse Events and Other (not including Serious) Adverse Events are reported for participants in the safety population (i.e., enrolled participants who took at least 1 dose of study drug and are the "population at risk"; N=503). For completeness, participants who were enrolled in the study but did not treat a PSVT episode with study drug are included under the Not Treated column

Additional Information

Cameron Szakacs _PhD_VP Drug Development

Milestone Pharmaceuticals Inc.

Phone: 1 704-594-4102

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place