Efficacy and Safety of Etripamil for the Termination of Spontaneous PSVT. NODE 301 [Part 1 and Part 2 (The RAPID Study)]

Efficacy and Safety of Etripamil for the Termination of Spontaneous PSVT. NODE 301 [Part 1 and Part 2 (The RAPID Study)]

Brief Summary:
This is a two-part, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil NS self-administered by patients who experience an episode of paroxysmal ventricular tachycardia (PSVT) in an at-home setting.

Part 1 comprised the conduct of the NODE-301 study up to the date of the adjudication of 150th positively adjudicated PSVT episode and Part 2 comprises the conduct of the NODE-301 study after the completion of Part 1.

The RAPID Study (NODE-301 - Part 2) will enroll patients enrolled during Part 1 who had not dosed with the double-blind study drug, or had not discontinued the study before the adjudication of the 150th positively adjudicated PSVT episode in Part 1, and patients enrolled into the study following the completion of Part 1. Enrollment will continue until and for approximately 6 months after the date of the adjudication of the 180th positively adjudicated PSVT episode.

The study will include the following visits: A Screening Visit, A Test Dose Randomization Visit, Monthly Follow-up Visits, A Randomized Treatment Period, A Randomized Treatment Period Follow-Up Visit, An Open-Label Treatment Period, and A Final Study Visit.

Detailed Description:
NODE-301 is a two-part, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of etripamil NS self-administered by patients who experience an episode of paroxysmal ventricular tachycardia (PSVT) in an at-home setting. Each episode 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 electrocardiogram (ECG).

This is an event-driven study. The study is comprised of 2 parts: Part 1 and Part 2.

Part 1 comprised the conduct of NODE-301 up to the date of the adjudication of the 150th positively adjudicated PSVT episode (January 15th, 2020). Part 1 had the same general study design as Part 2 of the study, with the key differences being that Part 2 includes a repeat dosing option during the randomized treatment phase, as well as during an added open-label treatment phase.

Part 2 (the RAPID Study) describes the conduct of NODE-301 following the completion of Part 1. RAPID will enroll patients enrolled during Part 1 who had not dosed with the double-blind study drug, or had not discontinued the study before the adjudication of the 150th positively adjudicated PSVT episode in Part 1, and patients enrolled into the study following the completion of Part 1.

Before randomization in the RAPID study, all patients will receive a test dose of an etripamil NS dosing regimen (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 patients on the study procedures.

The RAPID Study includes a Screening Visit, a Test Dose Randomization Visit, Monthly Follow-up Visits, a Randomized Treatment Period, a Randomized Treatment Period Follow-Up Visit, an Open-Label Treatment Period, and a Final Study Visit.

Study comprised of 4 arms:
- 2 arms consisting of patients enrolled during Part 1 randomized 2:1 to a single dose of study drug (etripamil NS 70 mg or placebo) to treat a perceived episode of PSVT
- 2 arms consisting of newly enrolled patients who pass a test dose regimen of etripamil NS 70 mg, randomized 1:1 to a dosing regimen of etripamil or placebo that allows patients to self-administer a second dose (not earlier than 10 minutes and not later than 15 minutes after the first dose) of study drug if symptoms are still present at 10 minutes, to treat a perceived PSVT episode.

Safety will be monitored during the treatment periods.

To ensure the safety of trial participants in RAPID, new processes or modification of listed processes may be put in place to reduce the risks associated with the COVID-19 pandemic. These potential changes include, but are not limited to, the use of tele-medicine to conduct study visit procedures, conduct of study procedures outside of the clinical site (i.e., at a patient's home) by site personnel or by trained but non-study personnel, and the distribution of investigational products by alternative secure delivery methods.


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Study comprised of 4 arms:
- 2 arms consisting of patients enrolled during Part 1 randomized 2:1 to a single dose of study drug (etripamil NS 70 mg or placebo) to treat a perceived episode of PSVT.
- 2 arms consisting of newly enrolled patients who pass a test dose regimen of etripamil NS 70 mg, randomized 1:1 to a dosing regimen of etripamil or placebo that allows patients to self-administer a second dose (not earlier than 10 minutes and not later than 15 minutes after the first dose) of study drug if symptoms are still present at 10 minutes, to treat a perceived PSVT episode.

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
RAPID study (NODE-301 Part 2) includes an open-label treatment phase following the randomized treatment phase of the study.

The study will include the following visits: A Screening Visit, A Test Dose Randomization Visit, Monthly Follow-up Visits, A Randomized Treatment Period, A Randomized Treatment Period Follow-Up Visit, An Open-Label Treatment Period, and A Final Study Visit. Patients who report no tolerability issues (i.e. adverse events) related to the study drug after having finished the Randomized Treatment Period, will be entered into the Open-Label Treatment Period while the patients who have not tolerated the double-blind study drug will pass to the Final Study Visit.

Patients comprising the single dose arms will not be entered into the open-label treatment phase of the RAPID study.

Primary Purpose: Treatment
Official Title: Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Efficacy, and Safety Study of Etripamil Nasal Spray for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia. NODE 301 Trial.
Actual Study Start Date: June 18, 2018
Estimated Primary Completion Date: January 2022
Estimated Study Completion Date: January 2022

Arm:
- Experimental: Etripamil 70 mg Single Dose
- Placebo Comparator: Placebo Single Dose
- Experimental: Etripamil 70 mg with Optional Second Dose
- Placebo Comparator: Placebo with Optional Second Dose

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