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

Paroxysmal Supraventricular Tachycardia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05410860
• Other study ID #: JX02002
• Secondary ID: CTR20221163
• Status: Recruiting
• Phase: Phase 3
• Start date: June 30, 2022
• Est. completion date: January 2025

Study information

• Verified date: September 2023
• Source: Ji Xing Pharmaceuticals (Shanghai) Co., Ltd.
• Contact: Qiu Deng
• Phone: +86-21-80311808
• Email: qiu.deng[@]jixingbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: January 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Paroxysmal Supraventricular Tachycardia
• Tachycardia
• Tachycardia, Supraventricular
• Tachycardia, Ventricular

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Baotou Central Hospital	Baotou
China	The First Affiliated Hospital of Baotou Medical College	Baotou
China	Beijing Anzhen Hospital; Capital Medical University	Beijing
China	Beijing Hospital	Beijing
China	Beijing Tongren Hospital, Capital Medical University	Beijing
China	Chui Yang Liu Hospital Affiliated to Tsinghua University	Beijing
China	Peking Union Medical College Hospital	Beijing
China	The Central Hospital of China Aerospace Corporation	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu
China	The First Hospital of Jilin University	Ch'ang-ch'un
China	The Third Xiangya Hospital of Central South University	Changsha
China	Xiangya Hospital, Central South University	Changsha
China	Changzhou No.2 People's Hospital	Changzhou
China	The First Affiliated Hospital of Chengdu Medical College	Chengdu
China	Affiliated Zhongshan Hospital of Dalian University	Dalian
China	People's Hospital of Deyang City	Deyang
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou
China	Nanfang Hospital of Southern Medical University	Guangzhou
China	Guizhou Provincial People's Hospital	Guiyang
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	The First People's Hospital of Hangzhou Linping District	Hangzhou
China	Zhejiang Provincial People's Hospital	Hangzhou
China	Huai'an First People's Hospital	Huai'an
China	Huainan First People's Hospital	Huainan
China	Huizhou Municipal Central Hospital	Huizhou
China	Jinan Central Hospital	Jinan
China	Shandong Province Qianfoshan Hospital	Jinan
China	The First Affiliated Hospital of Jinzhou Medical University	Jinzhou
China	Lanzhou University Second Hospital	Lanzhou
China	Lishui Municipal Central Hospital	Lishui
China	The First Affiliated Hospital of Henan Science and Technology University	Luoyang
China	Mianyang Central Hospital	Mianyang
China	The Nanchang Third Hospital	Nanchang
China	The Second Affiliated Hospital of Nanchang University	Nanchang
China	Jiangsu Province Hospital	Nanjing
China	Nanjing Drum Tower Hospital	Nanjing
China	Guangxi Zhuang Autonomous Region People's Hospital	Nanning
China	The second affiliated Hospital of Guangxi Medical University	Nanning
China	Nanyang Second General Hospital	Nanyang
China	Ningbo First Hospital	Ningbo
China	Ruijin Hospital of Shanghai Jiaotong University School of Medicine	Shanghai
China	Shanghai Pudong New Area People's Hospital	Shanghai
China	Shanghai Tongren Hospital	Shanghai
China	Shangrao People's Hospital	Shangrao
China	Shanxi Cardiovascular Hospital	Taiyuan
China	Jiangsu Taizhou People's Hospital	Taizhou
China	Binhai Hospital (Tianjin Fifth Central Hospital)	Tianjin
China	Tianjin Medical University General Hospital	Tianjin
China	CR and WISCO General Hospital	Wuhan
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan
China	Xingtai Third Hospital	Xingtai
China	The Fourth Affiliated Hospital Zhejiang University School of Medicine	Yiwu
China	ZiBo Central Hospital	Zibo

Sponsors (2)

Lead Sponsor	Collaborator
Ji Xing Pharmaceuticals (Shanghai) Co., Ltd.	Milestone Pharmaceuticals Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to conversion at time points of 5, 10, 15, 45, and 60 minutes		1 hour after administration of study drug
Secondary	Time to conversion in patients with the option of repeat administration		1 hour after administration of study drug
Secondary	The percentage of patients requiring additional medical intervention in emergency department to terminate an episode of PSVT		Up to 2 years
Secondary	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
Secondary	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
Secondary	The percentage of adverse event		Up to 2 years
Secondary	Number of participants with arrhythmias and conduction disorders detected on surface electrocardiogram(ECG) or cardiac monitoring system (CMS) recordings.		Up to 2 years