E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-operative atrial fibrillation (POAF) |
Fibrilación auricular posoperatoria (FAPO) |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of post-operative atrial fibrillation |
Prevención de fibrilación auricular posoperatoria |
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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 | PT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 |
To compare the efficacy of AGN-151607 with placebo to prevent post-operative atrial fibrillation (POAF) in participants who are undergoing open chest cardiac surgery |
Comparar la eficacia de AGN-151607 con la de un placebo para prevenir la fibrilación auricular posoperatoria (FAPO) en participantes sometidos a cirugía cardíaca de tórax abierto |
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E.2.2 | Secondary objectives of the trial |
- To compare the efficacy of AGN-151607 with placebo to reduce AF burden in participants who are undergoing open-chest cardiac surgery - To compare the efficacy of AGN-151607 with placebo to prevent POAF using alternative definitions for AF in participants who are undergoing open-chest cardiac surgery - To compare the safety of AGN-151607 with placebo in participants undergoing open-chest cardiac surgery |
- Comparar la eficacia de AGN-151607 con la de un placebo para reducir la carga de FA en participantes sometidos a cirugía cardíaca de tórax abierto - Comparar la eficacia de AGN-151607 con la de un placebo para prevenir la FAPO utilizando definiciones alternativas para la FA en participantes sometidos a cirugía cardíaca de tórax abierto - Comparar la seguridad de AGN-151607 con la de un placebo en participantes sometidos a cirugía cardíaca de tórax abierto |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 55 to 90 years of age, inclusive, at the time of signing the informed consent; - scheduled to undergo open-chest cardiac surgery (includes: coronary artery bypass graft [CABG] and/or valve repair/replacement); - in sinus rhythm for the last 48 hours prior to surgery (prior history of paroxysmal AF is acceptable); - willing to wear an electrocardiogram (ECG) patch for 30 days post-surgery and for 7 days after each study visit. |
- tener 55 a 90 años de edad, inclusive, en el momento de firmar el consentimiento informado; - tener programada una intervención de cirugía cardíaca de tórax abierto (incluye: derivación coronaria y/o valvuloplastia/sustitución valvular); - haber estado en ritmo sinusal durante las 48 horas previas a la intervención quirúrgica (se aceptan los antecedentes de FA paroxística); - estar dispuesto a utilizar un parche de electrocardiograma (ECG) durante 30 días después de la intervención quirúrgica y durante 7 días después de cada visita del estudio. |
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E.4 | Principal exclusion criteria |
- any medical condition that may put the participant at increased risk with exposure to botulinum toxin type A, including diagnosed muscular dystrophy (eg, Duchenne’s muscular dystrophy), myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, mitochondrial disease, or any other significant disease which might interfere with neuromuscular function; - participants with presence or history of any of the following within 3 months prior to the Day 1 visit that may indicate a vulnerable respiratory state per the investigator’s clinical judgment: aspiration pneumonia, lower respiratory tract infections, uncontrolled asthma, severe chronic obstructive pulmonary disease or otherwise compromised respiratory function; - permanent/persistent AF; - has a known allergy or sensitivity to any botulinum toxin type A preparation; - has a known allergy or sensitivity to medical adhesive (eg, ECG patch adhesive; hydrogel based adhesive); severe (> 55mm) atrial enlargement; left ventricular ejection fraction (LVEF) < 25%; - presence or history of symptomatic atrioventricular block > 1st degree within the last 30 days; - prior or concomitant therapy with Class I or III antiarrhythmic drugs unless proper washout was documented; - botulinum toxin type A (of any serotype) use within 6 months of randomization; - has been immunized for any botulinum toxin type A serotype as determined by participant medical history; - preoperative need for inotropes/vasopressors or intra-aortic balloon pump; - prior cardiac surgery; - history of ablation for AF; - planned ablation procedure for AF at the time of surgery; - emergency surgery; - impaired prognosis defined as EuroSCORE II greater than 7% perioperative mortality. |
- cualquier trastorno médico que pueda suponer un mayor riesgo para el participante con la exposición a la toxina botulínica de tipo A, tal como distrofia muscular diagnosticada (p. ej., distrofia muscular de Duchenne), miastenia grave, síndrome de Eaton-Lambert, esclerosis lateral amiotrófica, enfermedad mitocondrial o cualquier otra enfermedad importante que pueda interferir en la función neuromuscular; - los participantes con presencia o con antecedentes de cualquiera de los siguientes trastornos en los 3 meses previos a la visita del día 1, que podrían indicar un estado respiratorio vulnerable conforme al criterio clínico del investigador: neumonía aspirativa, infecciones respiratorias bajas, asma no controlada, enfermedad pulmonar obstructiva crónica grave u otra alteración de la función respiratoria; - FA permanente/persistente; - alergia o sensibilidad conocidas a la preparación de toxina botulínica de tipo A; - alergia o sensibilidad conocidas a los adhesivos médicos (p. ej., el adhesivo de los parches de ECG, adhesivos a base de hidrogel); dilatación auricular grave (> 55 mm); - fracción de eyección del ventrículo izquierdo (FEVI) < 25 %; - presencia o antecedentes de bloqueo auriculoventricular sintomático de segundo grado o mayor en los últimos 30 días; - tratamiento previo o concomitante con antiarrítmicos de clase I o III a menos que se haya documentado un período de lavado adecuado; - uso de toxina botulínica de tipo A (de cualquier serotipo) en los 6 meses previos a la aleatorización; - haber recibido inmunización para cualquier serotipo de la toxina botulínica de tipo A conforme a la anamnesis del participante; - necesidad preoperatoria de fármacos inotrópicos/vasopresores o de una bomba con balón intraaórtico; - cirugía cardíaca previa; antecedentes de ablación por FA; - ablación programada por FA en el momento de la cirugía; - cirugía de urgencia; - mal pronóstico definido como una puntuación EuroSCORE II > 7 % de mortalidad perioperatoria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of participants with at least 1 continuous atrial fibrillation (AF) episode ≥ 30 seconds during the first 30 days post surgery |
Porcentaje de participantes con al menos 1 episodio de fibrilación auricular (FA) continua ≥ 30 segundos durante los 30 primeros días después de la cirugía |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
within the first 30 days post surgery |
durante los 30 primeros días después de la cirugía |
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E.5.2 | Secondary end point(s) |
- Percentage of time spent in AF (AF burden) during the first 30 days post surgery - Percentage of participants with at least 1 event of symptomatic AF during the first 30 days post surgery - Time to first occurrence of AF during the first 30 days post surgery - Percentage of participants with at least 1 continuous AF episode ≥ 2 minutes during the first 30 days post-surgery - Percentage of participants with at least 1 continuous AF episode ≥ 5 minutes during the first 30 days post-surgery - Percentage of participants with at least 1 continuous AF episode ≥ 30 minutes during the first 30 days post-surgery - Percentage of participants with at least 1 continuous AF episode ≥ 1 hour during the first 30 days post surgery - Percentage of participants with at least 1 continuous AF episode ≥ 4 hours during the first 30 days post surgery - Percentage of participants with at least 1 continuous AF episode ≥ 24 hours during the first 30 days post surgery - Adverse events (AEs), physical examination, clinical laboratory tests, vital signs, electrocardiogram (ECGs), pulmonary function - Potential immunogenicity response |
- Porcentaje del tiempo transcurrido en FA (carga de FA) durante los 30 primeros días después de la cirugía - Porcentaje de participantes con al menos 1 episodio de FA sintomática durante los 30 primeros días después de la cirugía - Tiempo transcurrido hasta la primera aparición de FA durante los 30 primeros días después de la cirugía - Porcentaje de participantes con al menos 1 episodio de FA continua ≥ 2 minutos durante los 30 primeros días después de la cirugía - Porcentaje de participantes con al menos 1 episodio de FA continua ≥ 5 minutos durante los 30 primeros días después de la cirugía - Porcentaje de participantes con al menos 1 episodio de FA continua ≥ 30 minutos durante los 30 primeros días después de la cirugía - Porcentaje de participantes con al menos 1 episodio de FA continua ≥ 1 hora durante los 30 primeros días después de la cirugía - Porcentaje de participantes con al menos 1 episodio de FA continua ≥ 4 horas durante los 30 primeros días después de la cirugía - Porcentaje de participantes con al menos 1 episodio de FA continua ≥ 24 horas durante los 30 primeros días después de la cirugía |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
within the first 30 days post surgery |
durante los 30 primeros días después de la cirugía |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Austria |
Canada |
Germany |
Italy |
Netherlands |
Russian Federation |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
|
LVLS |
Última Visita Ultimo Sujeto |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |