Safety Study of Intranasal Etripamil for the Termination of Spontaneous Episodes of PSVT. NODE-302

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.

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 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.