Safety Study of Intranasal Etripamil for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia (PSVT). NODE-302
Condition: Paroxysmal Supraventricular Tachycardia
MeSH terms: Tachycardia; Tachycardia, Supraventricular; Tachycardia, Ventricular
Intervention: Etripamil NS 70 mg; Aptar Pharma Nasal Spray Bidose System
Intervention description: 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.
Intervention MeSH terms: Etripamil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 169.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Paroxysmal supraventricular tachycardia; cardiac monitoring; atrioventricular nodal reentrant tachycardia; atrioventricular reciprocating tachycardia; calcium channel blocker; conversion rate

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).
    

Eligibility criteria:

        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.