E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Paroxysmal Supraventricular Tachycardia |
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E.1.1.1 | Medical condition in easily understood language |
Sudden and unexpected episodes of rapid heartbeat that start and stop without warning due to an abnormality in the electrical system of the heart. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034044 |
E.1.2 | Term | Paroxysmal supraventricular tachycardia |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the safety of self-administered etripamil nasal spray (NS) outside of the clinical setting. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of self-administered etripamil NS outside of the clinical setting, and 2. To evaluate the impact of etripamil NS on PSVT disease burden, and 3. To evaluate the safety and efficacy of etripamil NS when used for multiple PSVT episodes
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Has been diagnosed with PSVT by a medical professional and reports having at least one previous episode of PSVT. For clarity, PSVT refers to episodic SVT that includes the AV node as a critical part of reentrant circuit. 2) Is of at least 18 years of age 3) Signed NODE-303 written informed consent 4) Women of child-bearing potential who are sexually active must be willing to use at least 1 form of contraception from the time of signed informed consent until 7 days after the last administration of study drug, and must be willing to discontinue from the study should they become or plan to become pregnant Approved forms of contraception include hormonal intrauterine devices or hormonal contraceptives (oral birth control pills, DepoProvera,patch, or other injectables) or single 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: a) Documented hysterectomy; b) Documented bilateral salpingectomy; or c) Documented bilateral oophorectomy; or d) Postmenopausal females, defined as having amenorrhea for at least 12 months without an alternative medical cause. All females who do not meet the above criteria are considered to be of childbearing potential. 5) Willing and able to comply with study procedures |
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E.4 | Principal exclusion criteria |
1) Patients with only a 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) are not eligible. Patients with a history of these tachycardias who are also diagnosed with PSVT are eligible. 2) History of allergic reaction to verapamil 3) Current therapy with digoxin, or any Class I or III antiarrhythmic drug. Patients may be eligible if these drugs are stopped at least five half-lives before the administration of etripamil NS. The only exception is amiodarone which must be stopped 30 days before enrollment. 4) History of ventricular pre-excitation, e.g., delta waves, Wolff-Parkinson-White syndrome. 5) History of a second- or third-degree AV block 6) Symptoms of congestive heart failure New York Heart Association Class II to IV 7) Significant physical or psychiatric condition including alcoholism or 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 8) History of syncope due to an arrhythmic etiology at any time, or history in last 5 years of unexplained syncope 9) Is pregnant or breastfeeding 10) Previously enrolled in a clinical trial for etripamil and received study drug 11) History of ACS or stroke within 6 months of screening 12) Evidence of renal dysfunction as determined by an estimated glomerular filtration rate assessed at the Screening Visit as follows: a) <60mL/min/1.73m2 for patients <60 years of age b) <40mL/min/1.73m2 for patients ≥60 and <70 years of age c) <35mL/min/1.73m2 for patients ≥70 years of age 13) SBP<90 mmHg 14) Has known allergies to adhesive materials or hydrogel used in the Cardiac Monitoring Device |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of participants presenting Adverse Events and/or number of participants with abnormal findings from the Cardiac Monitoring System recordings and physical examinations. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
It is estimated that 10 months will be needed to accrue enough documented self-administrations of etripamil NS in the safety database to meet regulatory requirements for the etripamil NS development program. When the criteria for concluding the study have been met, the Sponsor will announce a common study end date (CSED) for the entire study, and sites will be informed in advance to schedule all final patient visits prior to the CSED. The common study end date (CSED) for the entire study will depend on the rate of accrual of unique patients with an episode. |
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E.5.2 | Secondary end point(s) |
• Frequency of additional medical intervention to treat PSVT, as measured by emergency department (ED) visits, inpatient and outpatient hospital admissions, and concomitant medication use. • Improvement in patient quality of life, as measured by the Patient Reported Outcomes (PRO) System. • Patient satisfaction with treatment, as measured by the Treatment Satisfaction Questionnaire for Medication (TSQM-9) and other questions. • Termination of PSVT episodes (as measured by mean and median time to conversion and proportion of patients converting at at 3, 5, 10, 15, 20, 30, and 60 minutes after etripamil NS administration.) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
It is estimated that 10 months will be needed to accrue enough documented self-administrations of etripamil NS in the safety database to enable assessment of these endpoints. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 160 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Belgium |
Brazil |
Canada |
Chile |
Colombia |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
Israel |
Italy |
Mexico |
Netherlands |
Poland |
Romania |
Russian Federation |
Slovakia |
South Africa |
Spain |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |