Efficacy and Safety Study of Etripamil Nasal Spray Self-Administration for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia

Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Etripamil Nasal Spray Self-Administration for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia in Chinese Patients

To determine whether etripamil nasal spray (NS) self-administered by Chinese patients is superior to placebo at terminating episodes of PSVT in an at-home setting； To evaluate the efficacy of etripamil NS self-administered by Chinese patients compared with placebo on a range of clinical markers.

To evaluate the safety of etripamil NS self-administered by Chinese patients compared with placebo

Study Overview

• Status: Recruiting
• Conditions: Tachycardia, Supraventricular; Paroxysmal Supraventricular Tachycardia
• Intervention / Treatment: Drug: Placebo; Drug: Etripamil NS 70 mg

Detailed Description

The study is a 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 PSVT in an at-home setting.

This is an event-driven study. Enrollment into the study will continue until the adjudication of the 180th positively adjudicated PSVT episode in patients treated with double-blind study drug during the Randomized Treatment Period required for the study's pivotal analysis. After the date of the adjudication of the 180th positively adjudicated PSVT episode, all randomized patients will be unblinded at this timepoint and enter into an approximately 6 months open-label period of the study.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Qiu Deng; Phone Number: +86-21-80311808; Email: qiu.deng@jixingbio.com

Study Locations

• China
  • Baotou, China
    • Recruiting
    • The First Affiliated Hospital of BaoTou Medical College
  • Baotou, China
    • Recruiting
    • Baotou Central Hospital
  • Beijing, China
    • Not yet recruiting
    • Beijing Hospital
  • Beijing, China
    • Not yet recruiting
    • Peking Union Medical College Hospital
  • Beijing, China
    • Not yet recruiting
    • Beijing Tongren Hospital, Capital Medical University
  • Beijing, China
    • Not yet recruiting
    • The Central Hospital of China Aerospace Corporation
  • Beijing, China, 100032
    • Recruiting
    • Beijing Anzhen Hospital; Capital Medical University
  • Beijing, China
    • Recruiting
    • Chui Yang Liu Hospital Affiliated to Tsinghua University
  • Bengbu, China
    • Not yet recruiting
    • The First Affiliated Hospital of Bengbu Medical College
  • Ch'ang-ch'un, China
    • Recruiting
    • The First Hospital of Jilin University
  • Changsha, China
    • Recruiting
    • The Third Xiangya Hospital of Central South University
  • Changsha, China
    • Recruiting
    • Xiangya Hospital, Central South University
  • Changzhou, China
    • Recruiting
    • Changzhou No.2 People's Hospital
  • Chengdu, China
    • Recruiting
    • The First Affiliated Hospital of Chengdu Medical College
  • Dalian, China
    • Recruiting
    • Affiliated Zhongshan Hospital of Dalian University
  • Deyang, China
    • Recruiting
    • People's Hospital of Deyang City
  • Fuzhou, China
    • Recruiting
    • The First Affiliated Hospital Of Fujian Medical University
  • Guangzhou, China
    • Recruiting
    • Nanfang Hospital of Southern Medical University
  • Guiyang, China
    • Recruiting
    • Guizhou Provincial People's Hospital
  • Hangzhou, China
    • Not yet recruiting
    • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
  • Hangzhou, China
    • Not yet recruiting
    • Zhejiang Provincial People's Hospital
  • Hangzhou, China
    • Recruiting
    • The First People's Hospital of Hangzhou Linping District
  • Huai'an, China
    • Recruiting
    • Huai'an First People's Hospital
  • Huainan, China
    • Recruiting
    • Huainan First People's Hospital
  • Huizhou, China
    • Recruiting
    • Huizhou Municipal Central Hospital
  • Jinan, China
    • Recruiting
    • Jinan Central Hospital
  • Jinan, China
    • Not yet recruiting
    • Shandong province Qianfoshan hospital
  • Jinzhou, China
    • Recruiting
    • The First Affiliated Hospital of Jinzhou Medical University
  • Lanzhou, China
    • Recruiting
    • Lanzhou University Second Hospital
  • Lishui, China
    • Not yet recruiting
    • Lishui Municipal Central Hospital
  • Luoyang, China
    • Recruiting
    • The First Affiliated Hospital of Henan Science and Technology University
  • Mianyang, China
    • Recruiting
    • Mianyang Central Hospital
  • Nanchang, China
    • Recruiting
    • The Second Affiliated Hospital of Nanchang University
  • Nanchang, China
    • Recruiting
    • The Nanchang Third Hospital
  • Nanjing, China
    • Not yet recruiting
    • Nanjing Drum Tower hospital
  • Nanjing, China
    • Recruiting
    • Jiangsu Province Hospital
  • Nanning, China
    • Not yet recruiting
    • Guangxi Zhuang Autonomous Region People's Hospital
  • Nanning, China
    • Recruiting
    • The Second Affiliated Hospital of Guangxi Medical University
  • Nanyang, China
    • Recruiting
    • Nanyang second general hospital
  • Ningbo, China
    • Recruiting
    • Ningbo First Hospital
  • Shanghai, China
    • Recruiting
    • shanghai Tongren hospital
  • Shanghai, China
    • Recruiting
    • Ruijin Hospital of Shanghai Jiaotong University School of Medicine
  • Shanghai, China
    • Recruiting
    • Shanghai Pudong New Area People's Hospital
  • Shangrao, China
    • Not yet recruiting
    • Shangrao People's Hospital
  • Taiyuan, China
    • Recruiting
    • Shanxi Cardiovascular Hospital
  • Taizhou, China
    • Not yet recruiting
    • Jiangsu Taizhou People's Hospital
  • Tianjin, China
    • Not yet recruiting
    • Tianjin Medical University General Hospital
  • Tianjin, China
    • Recruiting
    • Binhai Hospital (Tianjin Fifth Central Hospital)
  • Wuhan, China
    • Recruiting
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Wuhan, China
    • Recruiting
    • CR and WISCO General Hospital
  • Xingtai, China
    • Recruiting
    • Xingtai Third Hospital
  • Yiwu, China
    • Recruiting
    • The Fourth Affiliated Hospital Zhejiang University School of Medicine
  • Zibo, China
    • Recruiting
    • Zibo central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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. Electrographically documented history of PSVT (e.g., diagnosis based on ECG , Holter monitoring, etc.). If patient had a prior ablation for PSVT, patient must have documented ECG evidence of PSVT post-ablation;
3. History of sustained episodes of PSVT (i.e., typically lasting 20 minutes or longer);

4. Females of childbearing potential who are sexually active with a male partner who is not surgically sterile (i.e., vasectomy) 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.;

   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 tubal ligation; or
     3. Documented bilateral oophorectomy; or
   • Postmenopausal females, defined as having amenorrhea for at least 12 months without an alternative medical cause; and
5. Signed written informed consent.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from participation in the study:

1. Systolic blood pressure (SBP) <90 mmHg after a 5-minute rest in sitting position at the Screening Visit or before the test dose. In patients treated with a chronic prophylactic drug for PSVT (e.g., beta blockers, verapamil, and diltiazem), the drug may be stopped for at least the equivalent of 5 half-lives, patients may be rescreened once, and chronic use of the drug cannot be restarted after randomization;
2. History of severe symptoms of hypotension, especially syncope, during episodes of PSVT;
3. History of atrial arrhythmia that does not involve the atrioventricular (AV) node as part of the tachycardia circuit (e.g., atrial fibrillation, atrial flutter, intra-atrial tachycardia);
4. History of allergic reaction to verapamil;
5. Current therapy with digoxin or any Class I or III antiarrhythmic drug, except if these drugs are stopped at least the equivalent of 5 half-lives before the Test Dose Randomization Visit;
6. Current chronic therapy with oral amiodarone, or have taken oral amiodarone within 30 days prior to the Test Dose Randomization Visit;
7. Evidence of ventricular pre-excitation (e.g., delta waves, short PR interval <100 msec, Wolff Parkinson White syndrome) on the ECG performed at the Screening Visit or before the test dose administration;
8. Evidence of a second- or third-degree AV block on the ECG performed at the Screening Visit or before the test dose administration;
9. History or evidence of severe ventricular arrhythmia (e.g., torsades de pointes, ventricular fibrillation, or ventricular tachycardia);
10. Current congestive heart failure defined by the New York Heart Association Class II to IV;
11. History of Acute Coronary Syndrome or stroke within 6 months of screening;
12. Evidence of hepatic dysfunction ;
13. Evidence of End-Stage Renal Disease;
14. Females who are pregnant or lactating;
15. Evidence or history of any significant physical or psychiatric condition including drug abuse, which, in the opinion of the Investigator, could jeopardize the safety of patients or affect their participation in the study. Additionally, the Investigator has the ability to exclude a patient if for any reason the Investigator judges the patient is not a good candidate for the study (e.g., illiteracy or poor understanding) or will not be able to follow study procedures;
16. Participation in any investigational drug or device study or the use of any investigational drug or device within 30 days or five terminal phase half-lives of the drug whichever is longer, prior to the Screening Visit; or
17. Previously enrolled in a clinical trial for Etripamil and received study drug during a perceived episode of PSVT;
18. An immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.

Before randomization in this study, all patients will receive a test dose of an etripamil NS dosing regimen.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etripamil NS 70 mg with Optional Second Dose; Dosing regimen that permits a second dose of Etripamil NS 70 mg	Drug: Etripamil NS 70 mg; Etripamil NS 70 mg will be administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.
Experimental: Placebo with Optional Second Dose; Dosing regimen that permits a second dose of placebo	Drug: Placebo; Placebo will be administered via the Aptar Pharma Nasal Spray Bidose System, supplied as prefilled devices packaged into child-resistant boxes with instructions for use provided in the study drug box.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to an adjudicated termination of a positively adjudicated episode of PSVT and conversion to sinus rhythm (SR) for at least 30 seconds within 30 minutes of start of study drug dosing	The primary efficacy endpoint is defined as an adjudicated termination of a positively adjudicated episode of PSVT (AV nodal reentrant tachycardia or AV reentrant tachycardia determination if possible) and conversion to sinus rhythm (SR) for at least 30 seconds within 30 minutes of start of study drug dosing.	Within 30 minutes of start of study drug dosing.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to conversion at time points of 5, 10, 15, 45, and 60 minutes		1 hour after administration of study drug
Time to conversion in patients with the option of repeat administration		1 hour after administration of study drug
The percentage of patients requiring additional medical intervention in emergency department to terminate an episode of PSVT		Up to 2 years
Number of participants with relief of specific symptoms (i.e., heart palpitations, rapid pulse feeling, chest pain, anxiety, shortness of breath, dizziness, and fainting)		1 hour after administration of study drug
Rating of Treatment Satisfaction Questionnaire for Medication (TSQM).	Treatment satisfaction will be analyzed by comparing the Treatment Satisfaction Questionnaire for Medication 9(TSQM-9) score for satisfaction in the 2 treatment groups. The TSQM-9 is composed of 9 questions with responses on a scale of 1 (extremely dissatisfied) to 7 (extremely satisfied). A higher score indicated greater satisfaction with medication.	1 hour after administration of study drug
The percentage of adverse event		Up to 2 years
Number of participants with arrhythmias and conduction disorders detected on surface electrocardiogram（ECG） or cardiac monitoring system (CMS) recordings.		Up to 2 years

Collaborators and Investigators

• Sponsor: Ji Xing Pharmaceuticals (Shanghai) Co., Ltd.
• Collaborators: Milestone Pharmaceuticals Inc.
• Investigators: Study Director: Lily Liu, Ji Xing Pharmaceuticals (Shanghai) Co., Ltd.; Principal Investigator: Changsheng Ma, Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: June 5, 2022
• First Submitted That Met QC Criteria: June 5, 2022
• First Posted (Actual): June 8, 2022

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Paroxysmal supraventricular tachycardia; Calcium channel blocker; Cardiac monitoring; Etripamil; Chinese patient; Conversion rate
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Tachycardia; Tachycardia, Ventricular; Tachycardia, Supraventricular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Etripamil
• Other Study ID Numbers: JX02002; CTR20221163 (Other Identifier: China CDE clinical trial registration)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes