Clinical trial NCT05410860: Efficacy and Safety Study of Etripamil Nasal Spray Self-Administration for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tachycardia, Supraventricular
Paroxysmal Supraventricular Tachycardia
Keywords: Etripamil
Paroxysmal supraventricular tachycardia
Cardiac monitoring
Calcium channel blocker
Conversion rate
Chinese patient
Lead sponsor: Corxel Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Milestone Pharmaceuticals Inc.
First posted: 2022-06-08
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients who pass the test dose of the Etripamil NS dosing regimen will be randomized in a 1:1 ratio to Etripamil NS 70mg or placebo using an Interactive Response Technology (IRT) system.
Primary purpose: TREATMENT

Brief 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

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.

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. 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.

Primary outcomes:
measure: 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
timeFrame: Within 30 minutes of start of study drug dosing.
Secondary outcomes:
measure: Time to conversion at time points of 5, 10, 15, 45, and 60 minutes
timeFrame: 1 hour after administration of study drug
measure: Time to conversion in patients with the option of repeat administration
timeFrame: 1 hour after administration of study drug
measure: The percentage of patients requiring additional medical intervention in emergency department to terminate an episode of PSVT
timeFrame: Up to 2 years
measure: Number of participants with relief of specific symptoms (i.e., heart palpitations, rapid pulse feeling, chest pain, anxiety, shortness of breath, dizziness, and fainting)
timeFrame: 1 hour after administration of study drug
measure: Rating of Treatment Satisfaction Questionnaire for Medication (TSQM).
timeFrame: 1 hour after administration of study drug
measure: The percentage of adverse event
timeFrame: Up to 2 years
measure: Number of participants with arrhythmias and conduction disorders detected on surface electrocardiogram（ECG） or cardiac monitoring system (CMS) recordings.
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Baotou
country: China
facility: Baotou Central Hospital
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College
city: Beijing
country: China
facility: Beijing Anzhen Hospital; Capital Medical University
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Beijing Tongren Hospital, Capital Medical University
city: Beijing
country: China
facility: Chui Yang Liu Hospital Affiliated to Tsinghua University
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: The Central Hospital of China Aerospace Corporation
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
city: Ch'ang-ch'un
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
city: Changzhou
country: China
facility: Changzhou No.2 People's Hospital
city: Chengdu
country: China
facility: The First Affiliated Hospital of Chengdu Medical College
city: Dalian
country: China
facility: Affiliated Zhongshan Hospital of Dalian University
city: Deyang
country: China
facility: People's Hospital of Deyang City
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
city: Hangzhou
country: China
facility: The First People's Hospital of Hangzhou Linping District
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
city: Huai'an
country: China
facility: Huai'an First People's Hospital
city: Huainan
country: China
facility: Huainan First People's Hospital
city: Huizhou
country: China
facility: Huizhou Municipal Central Hospital
city: Jinan
country: China
facility: Jinan Central Hospital
city: Jinan
country: China
facility: Shandong Province Qianfoshan Hospital
city: Jinzhou
country: China
facility: The First Affiliated Hospital of Jinzhou Medical University
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
city: Lishui
country: China
facility: Lishui Municipal Central Hospital
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan Science and Technology University
city: Mianyang
country: China
facility: Mianyang Central Hospital
city: Nanchang
country: China
facility: The Nanchang Third Hospital
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
city: Nanning
country: China
facility: Guangxi Zhuang Autonomous Region People's Hospital
city: Nanning
country: China
facility: The second affiliated Hospital of Guangxi Medical University
city: Nanyang
country: China
facility: Nanyang Second General Hospital
city: Ningbo
country: China
facility: Ningbo First Hospital
city: Shanghai
country: China
facility: Ruijin Hospital of Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Shanghai Pudong New Area People's Hospital
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
city: Shangrao
country: China
facility: Shangrao People's Hospital
city: Taiyuan
country: China
facility: Shanxi Cardiovascular Hospital
city: Taizhou
country: China
facility: Jiangsu Taizhou People's Hospital
city: Tianjin
country: China
facility: Binhai Hospital (Tianjin Fifth Central Hospital)
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wuhan
country: China
facility: CR and WISCO General Hospital
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Xingtai
country: China
facility: Xingtai Third Hospital
city: Yiwu
country: China
facility: The Fourth Affiliated Hospital Zhejiang University School of Medicine
city: Zibo
country: China
facility: ZiBo Central Hospital
Study officials:
affiliation: Corxel Pharmaceuticals
name: Xiaowen Chen
role: STUDY_DIRECTOR
affiliation: Beijing Anzhen Hospital
name: Changsheng Ma
role: PRINCIPAL_INVESTIGATOR
References: