Paroxysmal Supraventricular Tachycardia
Conditions
Keywords
Paroxysmal supraventricular tachycardia, cardiac monitoring, atrioventricular nodal reentrant tachycardia, atrioventricular reciprocating tachycardia, calcium channel blocker administered at home, conversion rate
Brief summary
This was a three-part, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil nasal spray (NS) self-administered by participants who experienced an episode of paroxysmal supraventricular tachycardia (PSVT) in an at-home setting. NODE-301 Part 1 included participants that received the randomized study drug to treat an episode of PSVT until the 150th positively adjudicated PSVT episode. Part 2 (also referred as the RAPID study) included participants that did not receive the randomized study drug in Part 1 and newly enrolled participants until the 180th positively adjudicated PSVT episode in Part 2. The study continued for approximately 6 months after the 180th positively adjudicated PSVT episode in Part 2 and this extension is referred to as Part 3 (also referred to as RAPID Extension).
Detailed description
NODE-301 was a three-part, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil NS self-administered by participants who experienced an episode of PSVT in an at-home setting. Each episode was documented by an ambulatory Cardiac Monitoring System (CMS) that was placed on the chest by the participants or caregiver when symptoms begin and recorded at least 5 hours of continuous electrocardiogram (ECG). This was an event-driven study. The study comprised of three parts: Parts 1, 2, and 3. NODE-301 Part 1 included participants that received the randomized study drug to treat an episode of PSVT until the 150th positively adjudicated PSVT episode (January 15th, 2020). Participants were randomized to etripamil 70 mg or placebo in a 2:1 ratio. Participants had a Test Dose Randomization Visit where they received 70 mg etripamil in sinus rhythm and a Treatment Period during which they could administer the randomized study drug during a perceived episode of PSVT. Part 2 (also referred as the RAPID study) included participants that did not use the randomized study drug to treat a perceived episode of PSVT before the Part 1 data cutoff and newly enrolled participants. Before randomization in the RAPID study, all participants received a Test Dose of etripamil consisting of an initial dose of etripamil 70 mg followed by a second dose of etripamil 70 mg 10 minutes later to evaluate tolerability and to train participants on the study procedures. After a successful Test Dose, participants in Part 2 were randomized to etripamil or placebo in a 1:1 ratio. When experiencing a PSVT episode, participants were instructed to administer a first dose of randomized study drug (70 mg etripamil or placebo) followed 10 minutes later, if PSVT symptoms persisted, by a second dose of study drug (70 mg etripamil or placebo). After having administered the randomized study drug for a perceived episode of PSVT, participants could enter an open-label period during which they had the possibility to treat a second episode of PSVT with open-label etripamil (70 mg etripamil with optional second dose of 70 mg etripamil). Part 2 continued until the 180th positively adjudicated PSVT episode (the data on which the primary efficacy analysis of RAPID was conducted) (July 20th 2022). The study continued for approximately 6 months after the 180th positively adjudicated PSVT episode in Part 2 and this extension is referred to as Part 3 (also referred to as RAPID Extension). The design of Parts 2 and 3 were the same and therefore their results are combined in this publication. NODE-301 study comprised 6 arms: * 2 arms consisting of participants enrolled in Part 1 that treated a perceived episode of PSVT with randomized study drug (etripamil NS 70 mg or placebo) in a 2:1 ratio. * 1 arm consisting of participants that only received the Test Dose in Part 1. * 2 arms consisting of participants enrolled in Parts 2 and 3 that treated a perceived episode of PSVT with randomized study drug (etripamil NS 70 mg with optional second dose of 70 mg etripamil or placebo) in a 1:1 ratio and could be enrolled in the open-label period to treat an additional PSVT episode with etripamil * 1 arm consisting of participants that only received the Test Dose in Parts 2 and 3.
Interventions
DRUGEtripamil
Etripamil administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.
DRUGPlacebo
Placebo administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.
DRUGEtripamil Test Dose
During the Test Dose, etripamil administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.
Sponsors
Medpace, Inc.
IQVIA Biotech
Milestone Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, care providers, investigators, and outcomes assessor were blinded to the treatment.
Intervention model description
NODE-301 study comprised 6 arms: * 2 arms consisting of participants enrolled in Part 1 that treated a perceived episode of PSVT with randomized study drug (etripamil NS 70 mg or placebo) in a 2:1 ratio. * 1 arm consisting of participants that only received the Test Dose in Part 1. * 2 arms consisting of participants enrolled in Parts 2 and 3 that treated a perceived episode of PSVT with randomized study drug (etripamil NS 70 mg with optional second dose of 70 mg etripamil or placebo) in a 1:1 ratio and could be enrolled in the open-label period to treat an additional PSVT episode with etripamil * 1 arm consisting of participants that only received the Test Dose in Parts 2 and 3.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants who met all of the following criteria were eligible to participate in the study: 1. Male or female participants at least 18 years of age; 2. Electrographically documented history of PSVT (e.g., electrocardiogram \[ECG\] obtained during an episode of PSVT, Holter monitoring, loop recorder, etc). If participant had a prior ablation for PSVT, participant had to have documented ECG evidence of PSVT post-ablation; 3. History of sustained episodes of PSVT (i.e., typically lasting approximately 20 minutes or longer); 4. Females of childbearing potential who were sexually active with a male partner who were not surgically sterile (i.e., vasectomy) had to agree to use a highly effective form of contraception from the time of signed informed consent until 30 days after the last administration of study drug. Females of childbearing potential had to have a negative serum pregnancy test result at the Screening Visit and at the Final Study Visit, a negative urine pregnancy test at the Test Dose Randomization Visit and had to use a highly effective form of contraception between the visits. The following categories defined females who were NOT considered to be of childbearing potential: * Premenopausal females with 1 of the following: 1. Documented hysterectomy, 2. Documented bilateral salpingectomy or tubal ligation; or 3. Documented bilateral oophorectomy, or * Postmenopausal females, defined as having amenorrhea for at least 12 months without an alternative medical cause; 5. Male participants, except those who were surgically sterile, had to use an approved highly effective form of contraception during the 3 days after any study drug administration; and 6. Signed written informed consent.
Exclusion criteria
Participants who met any of the following criteria were excluded from participation in the study: 1. Systolic blood pressure \<90 mmHg after a 5-minute rest in sitting position at the Screening Visit or before the Test Dose. In participants treated with a chronic prophylactic drug for PSVT (e.g., beta-blockers, verapamil, and diltiazem), the drug could be stopped for at least the equivalent of 5 half-lives, participants could be rescreened once, and chronic use of the drug could not be restarted after randomization; 2. History of severe symptoms of hypotension, especially syncope, during episodes of PSVT; 3. History of atrial arrhythmia that did not involve the AV node as part of the tachycardia circuit (e.g., atrial fibrillation, atrial flutter, intra-atrial tachycardia); 4. History of allergic reaction to verapamil; 5. Current therapy with digoxin or any Class I or III antiarrhythmic drug, except if these drugs were stopped at least the equivalent of 5 half-lives before the Test Dose Randomization Visit; 6. Current chronic therapy with oral amiodarone, or had taken oral amiodarone within 30 days prior to the Test Dose Randomization Visit; 7. Evidence of ventricular pre-excitation (e.g., delta waves, short PR interval \<100 msec, Wolff-Parkinson-White syndrome) on the ECG performed at the Screening Visit or before the Test Dose administration; 8. Evidence of a second- or third-degree AV block on the ECG performed at the Screening Visit or before the Test Dose administration; 9. History or evidence of severe ventricular arrhythmia (e.g., torsades de pointes, ventricular fibrillation, or ventricular tachycardia); 10. Current congestive heart failure defined by the New York Heart Association Class II to IV; 11. History of Acute Coronary Syndrome or stroke within 6 months of screening; 12. Evidence of hepatic dysfunction defined as alanine aminotransferase or aspartate aminotransferase \>3 × the upper limit of normal (ULN) or total bilirubin \>2 × ULN at the Screening Visit, unless due to Gilbert syndrome; 13. Evidence of End-Stage Renal Disease as determined by an estimated glomerular filtration rate assessed at the Screening Visit of \<15 mL/min/1.73m2, or requiring hemodialysis; 14. Females who were pregnant or lactating; 15. Evidence or history of any significant physical or psychiatric condition including drug abuse, which, in the opinion of the Investigator, could jeopardize the safety of participants, or affect their participation in the study. Additionally, the Investigator had the ability to exclude a participant if for any reason the Investigator judged the participant was not a good candidate for the study or would not be able to follow study procedures; 16. Participation in any investigational drug or device study or the use of any investigational drug or device within 30 days of the Screening Visit; or 17. Previously enrolled in a clinical trial for etripamil and received study drug during a perceived episode of PSVT. Before randomization in the study, all participants received a Test Dose of an etripamil NS dosing regimen (etripamil 70 NS mg in Part 1 and in Parts 2 and 3 an initial dose of etripamil NS 70 mg followed by a second dose of etripamil NS 70 mg not earlier than 10 minutes and not later than 15 minutes after the first dose) to evaluate tolerability and to train participants on the study procedures. Participants who passed the Test Dose were randomized in the NODE-301 (2:1) or RAPID and RAPID Extension (2:1) study. A failure of the Test Dose was considered if participants met any of the following criteria occurring after administration of the either the first or second dose of etripamil NS 70 mg: 1. Any symptoms consistent with clinically severe hypotension such as pre-syncope, medically significant lightheadedness, syncope, nausea, or vomiting; 2. For participants with a pre-Test Dose Systolic Blood Pressure above 100 mmHg: 1. Decrease in SBP ≥40 mmHg after Test Dose; or 2. Post-Test Dose SBP \<80 mmHg; 3. For participants with a pre-Test Dose SBP between 90 mmHg and 100 mmHg (inclusive): a) Post-Test Dose SBP \<75 mmHg; 4. Third-degree AV block, Mobitz II second-degree AV block, or Wenckebach with bradycardia ≤40 bpm; 5. New, significant sinus bradycardia Heart Rate ≤40 bpm or sinus pauses (≤3 seconds), if considered by the Investigator to put the participant's safety at risk if either were to occur while not under medical supervision; 6. Any new ventricular arrhythmia considered significant by the Investigator; or 7. Atrial fibrillation, atrial flutter or atrial tachycardia (event lasting longer than 30 seconds); 8. Refusal of second dose of etripamil Test Dose regimen. Participants who failed the Test Dose proceeded in the study as follows: * If the Investigator identified a possible reversible cause of the initial Test Dose failure (e.g., concomitant medication such as beta-blocker), a re-challenge with a new Test Dose of etripamil dose regimen was possible after elimination of the reversible cause (e.g., withdrawal of concomitant therapy with the appropriate washout period). Participants could be randomized if they passed the second Test Dose and the cause of the Test Dose failure was eliminated for the duration of the study; or * If the Investigator could not identify a reversible cause of the initial Test Dose failure, or if the potential cause could not be modified (e.g., necessary antihypertensive drug to control blood pressure), participants could not be randomized and completed a Final Study Visit. Participants who failed the Test Dose are part of the Test Dose Only Population.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | NODE-301 Part 1: Within 5 hours of start of study drug dosing. NODE-301 Parts 2 and 3: Within 30 minutes of start of study drug dosing. | The primary efficacy endpoint is defined as an adjudicated termination of a positively adjudicated episode of PSVT (AV nodal reentrant tachycardia or AV reentrant tachycardia determination if possible) and conversion to sinus rhythm (SR) for at least 30 seconds within 5 hours (NODE-301 Part 1), or 30 minutes (NODE-301 Parts 2 and 3) of start of study drug dosing. |
Countries
Belgium, Canada, France, Germany, Hungary, Netherlands, Poland, Spain, United States
Participant flow
Recruitment details
431 participants enrolled in Part 1 until the 150th positively adjudicated PSVT episode (15-Jan-2020). After the Part 1 cutoff, 82 participants enrolled in Part 1 transitioned to Part 2 in addition to 624 newly enrolled participants until the 180th positively adjudicated PSVT in Part 2 (20-Jul-2022). The study continued for about 6 months (Part 3) after the Part 2 cutoff with participants waiting for a PSVT episode to arise and 42 newly enrolled participants (27-Feb-2023).
Pre-assignment details
Participants had to pass a Test Dose before being randomized in the study. 431 participants received the etripamil 70 mg Test Dose before the Part 1 data cutoff. 672 participants received the RAPID etripamil 2x70mg Test Dose before the Part 2 cutoff; including 48 that transitioned from Part 1. An additional 42 participants received the RAPID etripamil 2x70mg Test Dose in Part 3. Participants failing the Test Dose due to safety/tolerability reasons were not randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 - Placebo Single Dose Self-administration of a single dose of placebo for a perceived episode of PSVT during the randomized treatment period. | 60 |
| Part 1 - Etripamil 70 mg Self-administration of a single dose of etripamil 70 mg for a perceived episode of PSVT during the randomized treatment period. | 138 |
| Part 1 - Test Dose Only Single Test Dose of etripamil 70 mg in sinus rhythm before randomization | 233 |
| Parts 2 and 3 - Placebo With Optional Second Dose of Placebo Self-administration of placebo for a perceived episode of PSVT followed 10 minutes later by an optional second dose of placebo, if symptoms persisted, during the randomized treatment period. | 143 |
| Parts 2 and 3 - Etripamil 70 mg With Optional Second Dose of Etripamil 70 mg Self-administration of etripamil 70 mg for a perceived episode of PSVT followed 10 minutes later by an optional second dose of etripamil 70 mg, if symptoms persisted, during the randomized treatment period. | 160 |
| Parts 2 and 3 - Test Dose Only (2X70 mg) Repeat Test Dose of etripamil 70 mg (2X70 mg) 10 minutes apart in sinus rhythm before randomization | 445 |
| Total | 1,179 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| NODE-301 Part 1 | Ablation | 0 | 0 | 16 |
| NODE-301 Part 1 | Adverse Event | 0 | 0 | 5 |
| NODE-301 Part 1 | Lost to Follow-up | 0 | 0 | 3 |
| NODE-301 Part 1 | Participants did not experienced PSVT before cutoff and did not enroll in Part 2 | 0 | 0 | 80 |
| NODE-301 Part 1 | Physician Decision | 0 | 0 | 4 |
| NODE-301 Part 1 | Protocol Violation | 0 | 0 | 2 |
| NODE-301 Part 1 | Reason was not provided by the participant | 0 | 0 | 15 |
| NODE-301 Part 1 | Test Dose Failure | 0 | 0 | 8 |
| NODE-301 Part 1 | Transitioned to Part 2 (RAPID) | 0 | 0 | 82 |
| NODE-301 Part 1 | Withdrawal by Subject | 0 | 0 | 18 |
| NODE-301 Part 2 and Part 3 | Ablation | 8 | 11 | 46 |
| NODE-301 Part 2 and Part 3 | Adverse Event | 1 | 3 | 14 |
| NODE-301 Part 2 and Part 3 | Lost to Follow-up | 1 | 0 | 7 |
| NODE-301 Part 2 and Part 3 | Physician Decision | 0 | 0 | 2 |
| NODE-301 Part 2 and Part 3 | Pregnancy | 0 | 0 | 1 |
| NODE-301 Part 2 and Part 3 | Prohibited Medication | 1 | 1 | 4 |
| NODE-301 Part 2 and Part 3 | Protocol Violation | 0 | 1 | 2 |
| NODE-301 Part 2 and Part 3 | Reason was not provided by the participant | 5 | 1 | 15 |
| NODE-301 Part 2 and Part 3 | Study Terminated by Sponsor | 46 | 61 | 314 |
| NODE-301 Part 2 and Part 3 | Test Dose failure | 0 | 0 | 8 |
| NODE-301 Part 2 and Part 3 | Withdrawal by Subject | 5 | 1 | 32 |
Baseline characteristics
| Characteristic | Part 1 - Placebo Single Dose | Part 1 - Etripamil 70 mg | Part 1 - Test Dose Only | Total | Parts 2 and 3 - Placebo With Optional Second Dose of Placebo | Parts 2 and 3 - Etripamil 70 mg With Optional Second Dose of Etripamil 70 mg | Parts 2 and 3 - Test Dose Only (2X70 mg) |
|---|---|---|---|---|---|---|---|
| Age, Continuous Part 1 | 55.0 years STANDARD_DEVIATION 14.96 | 57.2 years STANDARD_DEVIATION 13.58 | 54.1 years STANDARD_DEVIATION 15.59 | 55.2 years STANDARD_DEVIATION 14.92 | — | — | — |
| Age, Continuous Parts 2 and 3 | — | — | — | 53.9 years STANDARD_DEVIATION 14.1 | 55.9 years STANDARD_DEVIATION 12.5 | 52.2 years STANDARD_DEVIATION 13.9 | 53.9 years STANDARD_DEVIATION 14.9 |
| Age, Customized Part 1: Age at confirmation of PSVT (years) | 53.8 years STANDARD_DEVIATION 15.03 | 56.3 years STANDARD_DEVIATION 13.69 | 53.2 years STANDARD_DEVIATION 15.72 | 54.3 years STANDARD_DEVIATION 15.03 | — | — | — |
| Age, Customized Parts 2 and 3: Age at confirmation of PSVT (years) | — | — | — | 52.5 years STANDARD_DEVIATION 14.3 | 54.9 years STANDARD_DEVIATION 12.9 | 50.4 years STANDARD_DEVIATION 14.5 | 52.5 years STANDARD_DEVIATION 14.6 |
| Ethnicity (NIH/OMB) Part 1 Hispanic or Latino | 0 Participants | 5 Participants | 5 Participants | 10 Participants | — | — | — |
| Ethnicity (NIH/OMB) Part 1 Not Hispanic or Latino | 56 Participants | 129 Participants | 220 Participants | 405 Participants | — | — | — |
| Ethnicity (NIH/OMB) Part 1 Unknown or Not Reported | 4 Participants | 4 Participants | 8 Participants | 16 Participants | — | — | — |
| Ethnicity (NIH/OMB) Parts 2 and 3 Hispanic or Latino | — | — | — | 73 Participants | 12 Participants | 11 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Parts 2 and 3 Not Hispanic or Latino | — | — | — | 660 Participants | 129 Participants | 147 Participants | 384 Participants |
| Ethnicity (NIH/OMB) Parts 2 and 3 Unknown or Not Reported | — | — | — | 15 Participants | 2 Participants | 2 Participants | 11 Participants |
| Height Part 1 | 168.7 cm STANDARD_DEVIATION 9.12 | 168.8 cm STANDARD_DEVIATION 10.24 | 169.0 cm STANDARD_DEVIATION 9.7 | 169.0 cm STANDARD_DEVIATION 9.6 | — | — | — |
| Height Parts 2 and 3 | — | — | — | 169.4 cm STANDARD_DEVIATION 9.9 | 168.6 cm STANDARD_DEVIATION 9.4 | 168.7 cm STANDARD_DEVIATION 9.2 | 169.9 cm STANDARD_DEVIATION 10.2 |
| Number of participant reported emergency department visits for PSVT in lifetime Part 1 | 5.0 emergency department visits STANDARD_DEVIATION 13.17 | 2.7 emergency department visits STANDARD_DEVIATION 3.69 | 2.4 emergency department visits STANDARD_DEVIATION 3.2 | 2.8 emergency department visits STANDARD_DEVIATION 5.87 | — | — | — |
| Number of participant reported emergency department visits for PSVT in lifetime Parts 2 and 3 | — | — | — | 3.0 emergency department visits STANDARD_DEVIATION 9 | 3.6 emergency department visits STANDARD_DEVIATION 10.3 | 4.3 emergency department visits STANDARD_DEVIATION 14.2 | 2.3 emergency department visits STANDARD_DEVIATION 5.3 |
| Number of participant reported PSVT episodes in the past year Part 1 | 12.5 episodes STANDARD_DEVIATION 17.91 | 7.8 episodes STANDARD_DEVIATION 7.65 | 6.6 episodes STANDARD_DEVIATION 13.11 | 7.8 episodes STANDARD_DEVIATION 12.6 | — | — | — |
| Number of participant reported PSVT episodes in the past year Parts 2 and 3 | — | — | — | 6.7 episodes STANDARD_DEVIATION 14.5 | 10.0 episodes STANDARD_DEVIATION 21.1 | 6.8 episodes STANDARD_DEVIATION 15.1 | 5.7 episodes STANDARD_DEVIATION 11.3 |
| Participants with past ablation, n (%) No | — | — | — | 700 Participants | 132 Participants | 147 Participants | 421 Participants |
| Participants with past ablation, n (%) Yes | — | — | — | 48 Participants | 11 Participants | 13 Participants | 24 Participants |
| PSVT confirmation duration (years) Part 1 | 1.7 years STANDARD_DEVIATION 4.45 | 1.4 years STANDARD_DEVIATION 2.39 | 1.4 years STANDARD_DEVIATION 2.39 | 1.4 years STANDARD_DEVIATION 2.76 | — | — | — |
| PSVT confirmation duration (years) Parts 2 and 3 | — | — | — | 1.9 years STANDARD_DEVIATION 4.3 | 1.6 years STANDARD_DEVIATION 3.6 | 2.3 years STANDARD_DEVIATION 5.2 | 1.9 years STANDARD_DEVIATION 4.2 |
| Race (NIH/OMB) Part 1 American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants | — | — | — |
| Race (NIH/OMB) Part 1 Asian | 2 Participants | 5 Participants | 14 Participants | 21 Participants | — | — | — |
| Race (NIH/OMB) Part 1 Black or African American | 4 Participants | 6 Participants | 17 Participants | 27 Participants | — | — | — |
| Race (NIH/OMB) Part 1 More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Part 1 Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants | 4 Participants | — | — | — |
| Race (NIH/OMB) Part 1 Unknown or Not Reported | 2 Participants | 5 Participants | 6 Participants | 13 Participants | — | — | — |
| Race (NIH/OMB) Part 1 White | 51 Participants | 120 Participants | 194 Participants | 365 Participants | — | — | — |
| Race (NIH/OMB) Parts 2 and 3 American Indian or Alaska Native | — | — | — | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Parts 2 and 3 Asian | — | — | — | 15 Participants | 5 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Parts 2 and 3 Black or African American | — | — | — | 25 Participants | 3 Participants | 5 Participants | 17 Participants |
| Race (NIH/OMB) Parts 2 and 3 More than one race | — | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Parts 2 and 3 Native Hawaiian or Other Pacific Islander | — | — | — | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Parts 2 and 3 Unknown or Not Reported | — | — | — | 18 Participants | 4 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) Parts 2 and 3 White | — | — | — | 688 Participants | 131 Participants | 149 Participants | 408 Participants |
| Sex: Female, Male Part 1 Female | 39 Participants | 92 Participants | 142 Participants | 273 Participants | — | — | — |
| Sex: Female, Male Part 1 Male | 21 Participants | 46 Participants | 91 Participants | 158 Participants | — | — | — |
| Sex: Female, Male Parts 2 and 3 Female | — | — | — | 480 Participants | 100 Participants | 112 Participants | 268 Participants |
| Sex: Female, Male Parts 2 and 3 Male | — | — | — | 268 Participants | 43 Participants | 48 Participants | 177 Participants |
| Weight Part 1 | 83.99 Kg STANDARD_DEVIATION 20.994 | 82.45 Kg STANDARD_DEVIATION 23.787 | 83.80 Kg STANDARD_DEVIATION 24.149 | 83.39 Kg STANDARD_DEVIATION 23.571 | — | — | — |
| Weight Parts 2 and 3 | — | — | — | 81.6 Kg STANDARD_DEVIATION 19.4 | 82.7 Kg STANDARD_DEVIATION 19.4 | 81.1 Kg STANDARD_DEVIATION 19.9 | 81.4 Kg STANDARD_DEVIATION 19.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 138 | 0 / 233 | 0 / 143 | 0 / 160 | 1 / 445 |
| other Total, other adverse events | 39 / 60 | 98 / 138 | 151 / 233 | 114 / 143 | 127 / 160 | 324 / 445 |
| serious Total, serious adverse events | 1 / 60 | 1 / 138 | 4 / 233 | 3 / 143 | 2 / 160 | 18 / 445 |
Outcome results
Primary
The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration.
The primary efficacy endpoint is defined as an adjudicated termination of a positively adjudicated episode of PSVT (AV nodal reentrant tachycardia or AV reentrant tachycardia determination if possible) and conversion to sinus rhythm (SR) for at least 30 seconds within 5 hours (NODE-301 Part 1), or 30 minutes (NODE-301 Parts 2 and 3) of start of study drug dosing.
Time frame: NODE-301 Part 1: Within 5 hours of start of study drug dosing. NODE-301 Parts 2 and 3: Within 30 minutes of start of study drug dosing.
Population: In NODE-301 Part 1, the efficacy population consisted of 156 participants (37.2% of the 419 randomized participants).~In NODE-301 Parts 2 and 3, the efficacy population consisted of 214 participants (29.1% of the 735 randomized participants). The efficacy population was a modified intent-to-treat (mITT) population that included all participants who took study drug to treat an episode of perceived PSVT that was adjudicated by the Independent Adjudication Committee to be confirmed PSVT.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 - Placebo Single Dose | The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | Part 1: Participants converted to sinus rhythm within 5 hours | 36 Participants |
| Part 1 - Placebo Single Dose | The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | Part 1: Participants censored | 13 Participants |
| Part 1 - Etripamil 70 mg | The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | Part 1: Participants converted to sinus rhythm within 5 hours | 80 Participants |
| Part 1 - Etripamil 70 mg | The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | Part 1: Participants censored | 27 Participants |
| Parts 2 and 3 - Placebo With Optional Second Dose of Placebo | The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | Parts 2 and 3: Participants converted to sinus rhythm within 30 minutes | 30 Participants |
| Parts 2 and 3 - Placebo With Optional Second Dose of Placebo | The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | Parts 2 and 3: Participants censored | 70 Participants |
| Parts 2 and 3 - Etripamil 70 mg With Optional Second Dose of Etripamil 70 mg | The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | Parts 2 and 3: Participants censored | 39 Participants |
| Parts 2 and 3 - Etripamil 70 mg With Optional Second Dose of Etripamil 70 mg | The Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | Parts 2 and 3: Participants converted to sinus rhythm within 30 minutes | 75 Participants |
Comparison: In Part 1, participants who converted following medical assistance were censored at the time of conversion after medical assistance. Participants who presented missing data from time t to the end were censored at the time of last available data. Participants who did not convert or were not censored before 5 hours were censored at 5 hours.p-value: 0.121295% CI: [0.726, 1.623]Peto-Peto test
Comparison: In Parts 2 and 3, participants converting after additional medication interventions were censored after the end of the observation period.p-value: <0.00195% CI: [1.868, 4.371]Wilcoxon