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

NCT03635996 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: MSP-2017-1158
• Study Type: interventional
• Target: 169
• Locations: 2 countries
• Sites: 34

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).

Conditions

Paroxysmal Supraventricular Tachycardia

Keywords

Paroxysmal supraventricular tachycardia; cardiac monitoring; atrioventricular nodal reentrant tachycardia; atrioventricular reciprocating tachycardia; calcium channel blocker; conversion rate

Outcome Measures

Primary Outcomes (1)

• 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.

  18 months

Study Arms (1)

Etripamil NS 70 mg

EXPERIMENTAL

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

Drug: Etripamil NS 70 mg; Device: Aptar Pharma Nasal Spray Bidose System

Interventions

Etripamil NS 70 mg 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.

Also known as: MSP-2017

Etripamil NS 70 mg

Aptar Pharma Nasal Spray Bidose System 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.

Etripamil NS 70 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who meet all of the following criteria will be eligible to participate in the study:
• Male or female patients at least 18 years of age;
• Signed the NODE-302 written informed consent;
• 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;
• Willing and able to comply with all aspects of the study;
• 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:
• Documented hysterectomy,
• Documented bilateral salpingectomy, or
• Documented bilateral oophorectomy, or
• Postmenopausal females, defined as having amenorrhea for at least 12 months without an alternative medical cause; and
• 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.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from participation in the study, including but not limited to:
• 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);
• Any drug-related or procedure-related serious adverse event during the NODE-301 study;
• 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;
• 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;
• Systolic blood pressure \<90 mmHg after a 5-minute rest in sitting position at the NODE-302 Qualification Visit;
• Any symptoms consistent with clinically severe hypotension such as presyncope, medically significant lightheadedness, syncope, nausea, or vomiting;
• 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;
• 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;
• New symptoms of congestive heart failure defined by the New York Heart Association Class II to IV since randomization in the NODE-301 study;
• New stroke since randomization in the NODE-301 study;
• 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;
• New syncope since randomization in the NODE-301 study, especially if observed during the monitoring of the event treated in the NODE-301 study;
• 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;

Sponsors & Collaborators

• Milestone Pharmaceuticals Inc.: lead
• Medpace, Inc.: collaborator

Study Sites (34)

Arizona Arrhythmia Research Center

Phoenix, Arizona, 85016, United States

Location

Arkansas Cardiology

Little Rock, Arkansas, 72205, United States

Location

Los Alamitos Cardiovascular

Los Alamitos, California, 90720, United States

Location

South Denver Cardiology Associates, P.C

Littleton, Colorado, 80120, United States

Location

Baptist Health Ambulatory Services

Jacksonville, Florida, 32207, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Edgewater Medical Research

New Smyrna Beach, Florida, 32169, United States

Location

Piedmont Heart Institute

Atlanta, Georgia, 30309, United States

Location

Columbus Regional Research Institute

Columbus, Georgia, 31904, United States

Location

Georgia Arrythmia Consultants&Research Institute

Macon, Georgia, 312012, United States

Location

Iowa Heart Center

West Des Moines, Iowa, 50266, United States

Location

MedStar Health Research Institute

Baltimore, Maryland, 21237, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Atlantic Health System - Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

Trinity Medical WNY, PC

Buffalo, New York, 14215, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

The Presbyterian Hospital DBA Novant Health Heart and Vascular Institute

Charlotte, North Carolina, 28204, United States

Location

Heart House Research Foundation, LLC

Springfield, Ohio, 45505, United States

Location

Black Hills Cardiovascular Research

Rapid City, South Dakota, 57701, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Baylor Scott and White Research Institute - Round Rock

Round Rock, Texas, 78665, United States

Location

IHC Health Services Inc. DBA Intermountain Medical Center

Murray, Utah, 84157-7000, United States

Location

Libin Cardiovascular Institute of Alberta - University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

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

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Victoria Cardiac Arrhythmia Trials, Inc.

Victoria, British Columbia, V8T 1Z4, Canada

Location

University of Manitoba, St Boniface General Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Cambridge Cardiac Care Centre

Cambridge, Ontario, N1R 6V6, Canada

Location

Dawson Road Medical Centre

Guelph, Ontario, N1H 1B1, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8L 0A6, Canada

Location

Partners in Advanced Cardiac Evaluation (PACE) Cardiology Clinic

Newmarket, Ontario, M2R 3V6, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Montreal Heart Institute - Institut de Cardiologie de Montréal

Montreal, Quebec, H1T 1C8, Canada

Location

CIUSSS de l'Estrie - CHUS ; Hôpital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Related Publications (1)

• 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.

  PMID: 37753718 DERIVED

MeSH Terms

Conditions

Tachycardia, Ventricular; Tachycardia, Atrioventricular Nodal Reentry

Condition Hierarchy (Ancestors)

Tachycardia; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Tachycardia, Reciprocating

Results Point of Contact

• Title: Cameron Szakacs _PhD_VP Drug Development
• Organization: Milestone Pharmaceuticals Inc.

cszakacs@milestonepharma.com

1 704-594-4102

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: August 17, 2018
• Study Start: December 10, 2018
• Primary Completion: November 13, 2020
• Study Completion: November 13, 2020
• Last Updated: November 5, 2024
• Results First Posted: April 24, 2023

Record last verified: 2021-03

Locations

US (22); CA (12)