Safety Study of Intranasal Etripamil for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia (PSVT). NODE-302

NCT ID: NCT03635996

Last Updated: 2024-11-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 169 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-10
• Study Completion Date: 2020-11-13

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.

Conditions

Paroxysmal Supraventricular Tachycardia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Etripamil NS 70 mg

The dose of etripamil to be evaluated in NODE-302 is 70 mg.

Group Type: EXPERIMENTAL

Etripamil NS 70 mg

Intervention Type: DRUG

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.

Aptar Pharma Nasal Spray Bidose System

Intervention Type: DEVICE

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.

Interventions

Etripamil NS 70 mg

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.

Intervention Type: DRUG

Aptar Pharma Nasal Spray Bidose System

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 Type: DEVICE

Other Intervention Names

MSP-2017

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medpace, Inc.

INDUSTRY

Sponsor Role: collaborator

Milestone Pharmaceuticals Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arizona Arrhythmia Research Center

Phoenix, Arizona, United States

Arkansas Cardiology

Little Rock, Arkansas, United States

Los Alamitos Cardiovascular

Los Alamitos, California, United States

South Denver Cardiology Associates, P.C

Littleton, Colorado, United States

Baptist Health Ambulatory Services

Jacksonville, Florida, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Edgewater Medical Research

New Smyrna Beach, Florida, United States

Piedmont Heart Institute

Atlanta, Georgia, United States

Columbus Regional Research Institute

Columbus, Georgia, United States

Georgia Arrythmia Consultants&Research Institute

Macon, Georgia, United States

Iowa Heart Center

West Des Moines, Iowa, United States

MedStar Health Research Institute

Baltimore, Maryland, United States

Mayo Clinic

Rochester, Minnesota, United States

Atlantic Health System - Morristown Medical Center

Morristown, New Jersey, United States

Trinity Medical WNY, PC

Buffalo, New York, United States

Weill Cornell Medical Center

New York, New York, United States

The Presbyterian Hospital DBA Novant Health Heart and Vascular Institute

Charlotte, North Carolina, United States

Heart House Research Foundation, LLC

Springfield, Ohio, United States

Black Hills Cardiovascular Research

Rapid City, South Dakota, United States

Baylor College of Medicine

Houston, Texas, United States

Baylor Scott and White Research Institute - Round Rock

Round Rock, Texas, United States

IHC Health Services Inc. DBA Intermountain Medical Center

Murray, Utah, United States

Libin Cardiovascular Institute of Alberta - University of Calgary

Calgary, Alberta, Canada

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Vancouver General Hospital - Research Institute ; Gordon and Leslie Diamond Health Centre

Vancouver, British Columbia, Canada

Victoria Cardiac Arrhythmia Trials, Inc.

Victoria, British Columbia, Canada

University of Manitoba, St Boniface General Hospital

Winnipeg, Manitoba, Canada

Cambridge Cardiac Care Centre

Cambridge, Ontario, Canada

Dawson Road Medical Centre

Guelph, Ontario, Canada

Hamilton Health Sciences

Hamilton, Ontario, Canada

Partners in Advanced Cardiac Evaluation (PACE) Cardiology Clinic

Newmarket, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Montreal Heart Institute - Institut de Cardiologie de Montréal

Montreal, Quebec, Canada

CIUSSS de l'Estrie - CHUS ; Hôpital Fleurimont

Sherbrooke, Quebec, Canada

Countries

United States; Canada

References

Ip JE, Coutu B, Bennett MT, Pandey AS, Stambler BS, Sager P, Chen M, Shardonofsky S, Plat F, Camm AJ. Etripamil Nasal Spray for Conversion of Repeated Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia During Long-Term Follow-Up: Results From the NODE-302 Study. J Am Heart Assoc. 2023 Oct 3;12(19):e028227. doi: 10.1161/JAHA.122.028227. Epub 2023 Sep 27.

Reference Type: DERIVED

PMID: 37753718 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

MSP-2017-1158

Identifier Type: -

Identifier Source: org_study_id