E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Paroxysmal Supraventricular Tachycardia |
Tachicardia parossistica sopraventricolare (TPSV) |
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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. |
Episodi improvvisi e inaspettati di battito cardiaco accelerato che iniziano e si interrompono senza preavviso a causa di un'anomalia nel sistema elettrico del cuore. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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. |
L’obiettivo primario è valutare la sicurezza di etripamil spray nasale (SN) autosomministrato al di fuori del contesto clinico. |
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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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1. Valutare l’efficacia di etripamil SN autosomministrato al di fuori del contesto clinico; 2. Valutare l’impatto di etripamil SN sul carico di malattia nella TPSV; e 3. Valutare la sicurezza e l’efficacia di etripamil SN quando utilizzato per molteplici episodi di TPSV. |
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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 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 |
1)Ha ricevuto una diagnosi di TPSV da un medico professionista e riferisce di avere avuto almeno un precedente episodio di TPSV. Per chiarezza, TPSV si riferisce a tachicardia sopraventricolare (TSV) episodica che include il nodo atrio-ventricolare (AV) come parte fondamentale del circuito di rientro. 2)Ha almeno 18 anni di età. 3)Ha firmato il Consenso informato scritto per lo studio NODE-303. 4)Le donne in età fertile che sono sessualmente attive devono essere disposte a utilizzare almeno 1 metodo contraccettivo durante studio e devono essere disposte a ritirarsi dallo studio qualora dovessero iniziare una gravidanza o Appendice 5 Modulo da utilizzare per la gestione transitoria a seguito della sospensione dei sistemi informativi dell’OsSC a partire dal 1.1.2013 Agenzia Italiana del Farmaco - OsSC Pagina 17 di 46 pianificassero una gravidanza. 5)Disponibilità e capacità di attenersi alle procedure di studio. |
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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 |
1)I pazienti solo con anamnesi di aritmia atriale che non coinvolge il nodo atrioventricolare (AV) come parte del circuito tachicardico (ad es. fibrillazione atriale, flutter atriale, tachicardia intra-atriale) non sono idonei. I pazienti con un’anamnesi di queste tachicardie che presentano anche una diagnosi di TPSV sono idonei. 2)Anamnesi di reazione allergica a verapamil. 3)Attuale terapia con digossina o qualsiasi farmaco antiaritmico di classe I o III. I pazienti possono essere idonei se questi farmaci vengono interrotti almeno cinque emivite prima della somministrazione di etripamil SN. L’unica eccezione è costituita dall’amiodarone, che deve essere interrotto 30 giorni prima dell’arruolamento. 4)Anamnesi di pre-eccitazione ventricolare, ad es., onde delta, sindrome di Wolff- Parkinson-White. 5)Anamnesi di un blocco AV di secondo o terzo grado. 6)Sintomi di scompenso cardiaco congestizio di classe da II a IV in base alla New York Heart Association. 7)Condizione fisica o psichiatrica significativa tra cui alcolismo o abuso di farmaci che, a giudizio dello sperimentatore, potrebbe compromettere la sicurezza del paziente o impedirne la capacità di seguire le procedure dello studio. 8)Anamnesi di sincope dovuta a una eziologia aritmica in qualsiasi momento, o anamnesi negli ultimi 5 anni di sincope inspiegabile. 9)Gravidanza o allattamento al seno. 10)Precedente arruolamento in uno studio clinico per etripamil e assunzione del farmaco dello studio. 11)Anamnesi di sindrome coronarica acuta (SCA) o ictus entro 6 mesi dallo screening. 12)Evidenza di disfunzione renale, come determinato da un tasso stimato di filtrazione glomerulare valutato alla visita di screening come segue: a)<60 ml/min/1,73m2 per pazienti di età <60 anni; b)<40 ml/min/1,73m2 per pazienti di età =60 e <70 anni; c)<35 ml/min/1,73m2 per pazienti di età =70 anni. |
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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. |
Numero di partecipanti che presentano eventi avversi e / o numero di partecipanti con risultati anormali dalle registrazioni del sistema di monitoraggio cardiaco e dagli esami fisici. |
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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. |
Si stima che saranno necessari 10 mesi per accumulare un numero sufficiente di auto-somministrazioni documentate di etripamil NS nel database di sicurezza per soddisfare i requisiti normativi per il programma di sviluppo di etripamil NS. Quando i criteri per la conclusione dello studio sono stati soddisfatti, lo Sponsor annuncerà una data di fine studio comune (CSED) per l'intero studio e i siti saranno informati in anticipo per programmare tutte le visite finali del paziente prima del CSED. La data di fine dello studio comune (CSED) per l'intero studio dipenderà dal tasso di maturazione dei singoli pazienti con un episodio. |
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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.) |
• Frequency of additional medical intervention to treat PSVT, as measured by emergency department (ED) visits, inpatient and outpatient hospital Appendice 5 Modulo da utilizzare per la gestione transitoria a seguito della sospensione dei sistemi informativi dell’OsSC a partire dal 1.1.2013 Agenzia Italiana del Farmaco - OsSC Pagina 18 di 46 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. |
Si stima che saranno necessari 10 mesi per accumulare una documentazione sufficientemente documentata auto-somministrazione di etripamil NS nel database di sicurezza per consentire valutazione di questi endpoint. |
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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 | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Information not present in EudraCT |
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 |
Brazil |
Canada |
Chile |
Colombia |
Israel |
Mexico |
Russian Federation |
South Africa |
Ukraine |
United States |
Belgium |
Denmark |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Romania |
Slovakia |
Spain |
United Kingdom |
Czechia |
Argentina |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 24 |
E.8.9.2 | In all countries concerned by the trial days | 0 |