Paroxysmal Supraventricular Tachycardia
Conditions
Keywords
Paroxysmal supraventricular tachycardia, cardiac monitoring, atrioventricular nodal reentrant tachycardia, atrioventricular reciprocating tachycardia, calcium channel blocker, conversion rate
Brief summary
The primary objective of this study is to evaluate the safety of etripamil nasal spray (NS) 70 mg when self-administered by patients with an episode of Paroxysmal Supraventricular Tachycardia in an outpatient setting (i.e., without medical supervision).
Detailed description
The NODE-302 study is an extension of the NODE-301 efficacy study. It is a multi-centre, open label study designed to evaluate the safety of etripamil NS 70 mg when self-administered by patients for spontaneous episodes of PSVT in an outpatient setting. All patients randomized in the NODE-301 study and who meet the inclusion and exclusion criteria of the NODE-302 study are eligible for the NODE-302 study. After each episode of PSVT, patients will have the option to continue in the NODE-302 study and manage subsequent episodes of PSVT with etripamil NS 70 mg if they do not meet any withdrawal criteria. Each episode of PSVT will be documented by an ambulatory cardiac monitoring system (CMS) that will be placed on the chest by the patient or caregiver when symptoms begin, and will record at least 5 hours of continuous ECG. The study will include a Qualification Visit, a Treatment Period(s) , a Follow-up Visit(s) ,a Final Study Visit and if necessary an Early Termination Visit if the patient withdraws from the study after taking etripamil NS 70 mg and had a Follow-up Visit, or the patient withdraws from the study and did not take etripamil NS 70 mg.
Interventions
All patients will receive a total of 200 micro-liters of etripamil NS 70 mg via the Aptar Pharma Nasal Spray Bidose System each time they self-administer study drug.
Patients will self-administer the study drug using the Aptar Pharma Nasal Spray Bidose System. The devices will be prefilled and packaged into child-resistant boxes.Instructions for its use will be provided in the study drug box.
Sponsors
Medpace, Inc.
Milestone Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients who meet all of the following criteria will be eligible to participate in the study: 1. Male or female patients at least 18 years of age; 2. Signed the NODE-302 written informed consent; 3. Previously randomized in the NODE-301 study: * Received the study drug to treat symptoms the patient believed were consistent with an episode of PSVT during the NODE-301 study, irrespective of the study drug efficacy; OR * Did not experience an episode of PSVT or did not use the study drug at the time of the NODE-301 study completion; 4. Willing and able to comply with all aspects of the study; 5. Females of childbearing potential who are sexually active must agree to use an approved 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 should have a negative urine pregnancy test result at the Qualification Visit and at the Follow-up Visit(s), and must use an approved form of contraception between the 2 visits. Approved forms of contraception include hormonal intrauterine devices and hormonal contraceptives (oral birth control pills, Depo Provera®, patch, or other injectables) together with supplementary double barrier methods, such as condoms or diaphragms with spermicidal gel or foam; The following categories define females who are NOT considered to be of childbearing potential: * Premenopausal females with 1 of the following: 1. Documented hysterectomy, 2. Documented bilateral salpingectomy, or 3. Documented bilateral oophorectomy, or * Postmenopausal females, defined as having amenorrhea for at least 12 months without an alternative medical cause; and 6. Male patients, except those who are surgically sterile, must use an approved highly effective form of contraception during the 3 days after study drug administration.
Exclusion criteria
Patients who meet any of the following criteria will be excluded from participation in the study, including but not limited to: 1. Evidence of new severe arrhythmia discovered since the NODE-301 Test Dose Randomization Visit, including those reported on the Cardiac Monitoring System (CMS) report of the outpatient PSVT event treated with the study drug in the NODE 301 study: d. Third-degree Atrioventricular (AV) block, Mobitz II second-degree AV block, or Wenckebach with bradycardia ≤40 bpm; e. Significant symptomatic sinus bradycardia heart rate (HR) ≤40 bpm or sinus pauses (≥3 seconds); f. Any significant ventricular arrhythmia (premature ventricular beats and couplets \[\>6 premature ventricular contractions per 45 seconds electrocardiogram (ECG)\] are considered significant); or g. Atrial fibrillation (event lasting longer than 30 seconds); 2. Any drug-related or procedure-related serious adverse event during the NODE-301 study; 3. Any severe adverse event (AE) in the NODE-301 study that was severe enough to preclude administration of etripamil NS 70 mg in the NODE-302 study; 4. Any new drug prescribed after the end of the patient's participation in the NODE-301 study that could lower blood pressure or decrease AV node conduction; 5. Systolic blood pressure \<90 mmHg after a 5-minute rest in sitting position at the NODE-302 Qualification Visit; 6. Any symptoms consistent with clinically severe hypotension such as presyncope, medically significant lightheadedness, syncope, nausea, or vomiting; 7. New therapy with digoxin, amiodarone, or any Class I or III antiarrhythmic drug added after the end of the patient's participation in the NODE-301 study; 8. New evidence of ventricular pre-excitation (e.g., delta waves, short PR interval, Wolff Parkinson-White syndrome) on the ECG since randomization in the NODE-301 study; 9. New symptoms of congestive heart failure defined by the New York Heart Association Class II to IV since randomization in the NODE-301 study; 10. New stroke since randomization in the NODE-301 study; 11. New evidence of a significant physical or psychiatric condition including drug abuse, which in the opinion of the Investigator, could jeopardize the safety of the patient, or impede the patient's capacity to follow the study procedures since randomization in the NODE-301 study; 12. New syncope since randomization in the NODE-301 study, especially if observed during the monitoring of the event treated in the NODE-301 study; 13. New evidence of hepatic dysfunction defined as alanine aminotransferase or aspartate aminotransferase \>3 × the upper limit of normal (ULN) or total bilirubin \>2 × ULN, unless due to Gilbert syndrome observed at the NODE-302 Qualification Visit; 14. New evidence of renal dysfunction as determined by an estimated glomerular filtration rate assessed at the NODE-302 Qualification Visit as follows: 1. \<60 mL/min/1.73 m2 for patients \<60 years of age, 2. \<40 mL/min/1.73 m2 for patients ≥60 and \<70 years of age, or 3. \<35 mL/min/1.73 m2 for patients ≥70 years of age; 15. Participation in any investigational drug or device study or the use of any investigational drug or device since the Final Study Visit in the NODE-301 study. Withdrawal Criteria Patient participation in this clinical study may be discontinued for any of the following reasons: * The patient withdraws consent or requests discontinuation from the study for any reason; * The patient took the study drug in both the NODE-301 and the NODE-302 studies for symptoms not associated with an episode of PSVT; * Occurrence of any medical condition, AE, or circumstance that exposes the patient to substantial risk and/or does not allow the patient to adhere to the requirements of the protocol; * Requirement of a prohibited concomitant medication and/or change in the use of chronic therapies, such as concomitant beta-blockers, calcium channel blockers, and medications that can lower blood pressure; * Patient failure to comply with protocol requirements or study-related procedures; * Termination of the study by Milestone or a regulatory authority; or * The patient self-administered a total of 11 doses of etripamil Nasal Spray 70 mg in the NODE-302 study. Patients who withdraw from the study after taking etripamil Nasal Spray 70 mg and had a Follow-up Visit will be required to undergo an Early Termination Visit. Patients who withdraw from the study and did not take etripamil Nasal Spray 70 mg will be required to undergo an Early Termination Visit. Patients who withdraw after taking the study drug but did not have a Follow-up Visit will be required to undergo a Final Study Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | 18 months | The efficacy analyses were performed on the Efficacy Population. The primary efficacy variable was the time to conversion of an episode of PSVT to SR after study drug administration. |
Countries
Canada, United States
Participant flow
Recruitment details
All patients randomized in Part 1 of the NODE-301 study and who met the inclusion and exclusion criteria of the NODE-302 study were eligible for the NODE-302 study. This study was conducted only at clinical sites that participated in the NODE-301 Part 1 study. Study was initiated on December 10, 2018 and completed on November 13, 2020.
Pre-assignment details
Of the 169 patients enrolled, 64 (37.9%) of 169 patients did not treat an episode with etripamil in this study.
Participants by arm
| Arm | Count |
|---|---|
| Etripamil NS 70 mg The dose of etripamil evaluated in NODE-302 was 70 mg.
Etripamil NS 70 mg: All patients received a total of 200 micro-liters of etripamil NS 70 mg via the Aptar Pharma Nasal Spray Bidose System each time they self-administer study drug.
Aptar Pharma Nasal Spray Bidose System: Patients were self-administer the study drug using the Aptar Pharma Nasal Spray Bidose System. The devices were be prefilled and packaged into child-resistant boxes. Instructions for its use was provided in the study drug box. | 105 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ablation | 26 |
| Overall Study | Adverse Event | 7 |
| Overall Study | Did not meet eligibility criteria | 5 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Prohibited medication | 5 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Site closure (2), compliance with IP, directed by sponsor and site termination. | 5 |
| Overall Study | Study terminated by Sponsor | 94 |
| Overall Study | Withdrawal by Subject | 20 |
Baseline characteristics
| Characteristic | Etripamil NS 70 mg |
|---|---|
| Age, Continuous Age at confirmation of PSVT | 57.2 years STANDARD_DEVIATION 13.79 |
| Age, Continuous Age at informed consent signed | 58 years STANDARD_DEVIATION 13.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 100 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Number of patient-reported emergency department visits for PSVT in lifetime | 2.7 emergency department visits STANDARD_DEVIATION 2.74 |
| Number of patient-reported PSVT episodes in the year prior to NODE-301 | 9.7 episodes STANDARD_DEVIATION 11.79 |
| PSVT confirmation duration (years) | 1.3 years STANDARD_DEVIATION 1.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 87 Participants |
| Sex: Female, Male Female | 65 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 105 |
| other Total, other adverse events | 67 / 105 |
| serious Total, serious adverse events | 8 / 105 |
Outcome results
Primary
Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration.
The efficacy analyses were performed on the Efficacy Population. The primary efficacy variable was the time to conversion of an episode of PSVT to SR after study drug administration.
Time frame: 18 months
Population: Primary analysis of the primary efficacy endpoint for each patient's first episode of PSVT confirmed by adjudication and treated with etripamil NS 70 mg. There were 92 patients who had a PSVT episode that was confirmed by adjudication and were included in the primary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Etripamil NS 70 mg | Time to Conversion of an Episode of PSVT to Sinus Rhythm (SR) After Study Drug Administration. | 21.1 minutes |