E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IV unresectable, recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC) |
Cancer de pulmon de celulas no pequeñas y no escamosas (CPNMne) en estadio IV, irresecable, recidivante o metastasico |
|
E.1.1.1 | Medical condition in easily understood language |
A certain common kind of inoperable, recurrent or metastatic Lung cancer. |
Un tipo comun de cancer de pulmon inoperable, recurrente o metastasico |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
Compare the overall response rate (ORR) of MYL-1402O with that of Avastin, in combination with CP chemotherapy during the first 18 weeks of first-line treatment in patients with Stage IV nsNSCLC |
Comparar la tasa de respuesta global (TRG) de MYL-1402O con la de Avastin, en combinación con la quimioterapia de CP durante las primeras 18 semanas del tratamiento de primera línea, en pacientes con CPNMne en estadio IV. |
|
E.2.2 | Secondary objectives of the trial |
1. Assess the safety profile of MYL-1402O as compared with that of Avastin when administered in combination with CP as first-line treatment for Stage IV nsNSCLC and when administered alone in the maintenance setting 2. Assess other efficacy parameters: Disease Control Rate (DCR), Duration of Response (DR), Time To Progression (TP), Progression-Free survival (PFS), and Overall Survival (OS) of MYL-1402O as compared to Avastin when administered in combination with CP as first-line treatment for Stage IV nsNSCLC 3. Assess the potential immunogenicity at Week 18 and 42 of treatment of MYL-1402O as compared with that of Avastin 4. Compare the pharmacokinetic (PK) profile of MYL-1402O and Avastin using a population PK (PopPK) approach |
1. Evaluar el perfil de seguridad de MYL-1402O en comparación con el de Avastin cuando se administra en combinación con CP como tratamiento de primera línea para el CPNMne en estadio IV y cuando se administra en monoterapia en el contexto de mantenimiento. 2. Evaluar otros parámetros de la eficacia: tasa de control de la enfermedad (TCE), duración de la respuesta (DR), tiempo hasta la progresión (TP), supervivencia sin progresión (SSP) y supervivencia global (SG) de MYL-1402O en comparación con Avastin cuando se administran en combinación con CP como tratamiento de primera línea para el CPNMne en estadio IV. 3. Evaluar la posible inmunogenia en las semanas 18 y 42 de tratamiento de MYL-1402O en comparación con la de Avastin. 4. Comparar el perfil farmacocinético (FC) de MYL-1402O y Avastin usando un enfoque de FC poblacional (FCpob). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Has demonstrated the ability to understand verbal and/or written instructions, to provide written informed consent, and is capable and agreeable to comply with protocol requirements. 2. Male or female at least 18 years of age at the time of signing an informed consent form. 3. Has a documented imaging diagnosis of Stage IV unresectable, recurrent or metastatic nsNSCLC. 4. Has documented histologic or cytologic diagnosis of advanced nsNSCLC with negative or unknown sensitizing epidermal growth factor receptor (EGFR) mutation, and negative or unknown echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement. 5. Has measurable disease with at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1; Section 12.1 [Appendix A]). All target (up to 5 lesions) and nontarget lesions (other measurable not included in target, nonmeasurable, nonevaluable, or evaluable lesions) should be included in the assessment or evaluation of disease response as defined by RECIST 1.1 (Eisenhauer et al 2009). 6. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale. 7. Has at least 6 months of expected survival. 8. Has not received any prior systemic therapy for first-line treatment of advanced lung cancer, except adjuvant chemotherapy, and remained disease-free for at least 12 months from time 9. May have had prior radiation therapy provided <25% of bone marrow is involved (Section 12.3 [Appendix C]), except for previous mediastinal irradiation that is not allowed. a. Prior radiation therapy must have been completed at least 2 weeks prior to Day 0 of Cycle 1 b. Patient must have recovered from acute toxicities associated with radiation therapy. Radiation-related toxicities must have resolved to Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 4.03) grade prior to Day 0 of Cycle 1. 10. May have brain metastasis provided the metastasis has been treated and is considered stable at the time of signing the informed consent form. Treated, stable brain metastasis is defined as: a. Metastasis having no evidence of progressive disease (PD) or hemorrhage after treatment. b. No ongoing requirement for dexamethasone, as ascertained by clinical examination and post-treatment brain imaging (computed tomography [CT] scan or magnetic resonance imaging [MRI]) at baseline. c. Anticonvulsants are allowed, provided the dose regimen has been unchanged (stable) for at least 2 weeks prior to patient signing informed consent. d. Treatment for brain metastasis may include whole brain radiotherapy, radiosurgery (Gamma Knife®, linear particle accelerator, or equivalent), or a combination thereof, as deemed appropriate by the treating physician. All brain metastasis treatments must be completed at least 14 days prior to Day 0 of Cycle 1. 11. Has adequate organ functions based on the following: a. Bone marrow reserve: i. White blood cell count ≥3 × 103/μL; ii. Absolute neutrophil count (segmented and bands) ≥1.5 × 103/μL; iii. Platelet count ≥100 × 103/μL; iv. Hemoglobin ≥9.0 g/dL with at least 2 weeks without transfusions before Day 0 of Cycle 1. b. Hepatic: i. Total bilirubin ≤1.5 × upper limit of normal (ULN); except if elevation is due to Gilbert’s Syndrome with transitory elevations of indirect bilirubin. ii. Alkaline phosphatase, alanine transaminase, and/or aspartate transaminase ≤3 × ULN. Significant levels of alanine transaminase or aspartate transaminase should be further assessed for viral hepatitis. (Note: Isolated alkaline phosphatase elevation beyond 3 × ULN due to bone metastasis is allowed). c. Renal: i. Calculated creatinine clearance ≥45 mL/min based on the original, weight-based Cockcroft and Gault formula (Cockcroft and Gault 1976; Section 12.4 [Appendix D]) ii. Urine protein to creatinine ratio ≤1. A patient with urine protein to creatinine ratio > 1 may be enrolled if ≤2g of protein in 24-hour urine collection. 12. If capable of reproduction, patients and their partners must use contraceptive methods during the full duration of the study and for 6 months after discontinuation of study. A patient who is capable of reproduction must be willing to practice birth control by using 2 different highly effective double barrier methods of contraception, or abstinence from sexual intercourse for the duration of the study. In particular a female patient of childbearing potential must use a method that results in less than 1% failure rate per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or vasectomized partner. A male patient of reproductive potential (defined as a male that has not had a vasectomy) must use a condom with spermicide and their female partner to use another highly effective form of contraception. |
1.Ha demostrado capacidad para comprender las instrucciones por escrito y/o oral, para proporcionar el consentimiento informado por escrito, y es capaz de cumplir los requisitos del protocolo y está conforme con ello. 2.Varón o mujer al menos 18 años edad en el momento de firma delconsentimiento. 3.Tiene diagnóstico documentado por técnicas de imagen de CPNMne en estadio IV, irresecable, recidivante o metastásico. 4.Tiene diagnóstico citológico o histológico documentado de CPNMne avanzado con mutación sensibilizante negativa o desconocida del receptor del factor de crecimiento epidérmico (EGFR), y reordenamiento negativo o desconocido de cinasa del linfoma anaplásico y proteína 4 asociada a microtúbulos equinodermos (EML4-ALK). 5.Tiene enfermedad medible con al menos 1 lesión según Criterios de evaluación de respuesta en tumores sólidos (RECIST 1.1; apartado 12.1 [Anexo A]). Todas las lesiones diana (hasta 5) y no diana (otras lesiones no incluidas en las diana, no medibles, no evaluables o evaluables) deberán incluirse en la evaluación de la respuesta de la enfermedad según definición en los RECIST 1.1 (Eisenhauer et al 2009). 6. Tiene un estado funcional de 0 o 1 según escala del Grupo Coop. de Oncología del Este. 7.Tiene al menos 6 meses expectativa supervivencia. 8.No ha recibido ningún tratamiento sistémico previo como tratamiento de primera línea del cáncer de pulmón avanzado, excepto quimioterapia adyuvante, y se mantuvo libre de la enfermedad durante al menos 12 meses 9.Podrá haber recibido radioterapia previa siempre que la afectación de la médula ósea sea <25 % (apartado 12.3[Anexo C]), excepto la radioterapia previa del mediastino que no está permitida. a.La radioterapia previa debe haberse finalizado al menos 2 semanas antes del día 0 del ciclo 1; b.El paciente debe haberse recuperado de los efectos secundarios agudos asociados a radioterapia. Los efectos secundarios relacionados con radiación deben haberse resuelto hasta el grado 1, conforme a Criterios de terminología común para acontecimientos adversos del Inst. Nacional del Cáncer, antes del día 0 del ciclo 1. 10.Puede tener metástasis cerebral siempre que haya sido tratada y se considere estable en el momento de la firma del consentimiento. La metástasis cerebral tratada y estable se define como: a.Metástasis que no presenta indicios de progresión de la enfermedad (PE) o hemorragia tras el tratamiento; b.No es necesaria la dexametasona en este momento, según exploración clínica y las técnicas de imagen del cerebro postratamiento TAC o resonancia RM] en el periodo basal;c.Se permiten anticonvulsivos siempre que la pauta posológica se mantenga sin cambios (estable) durante al menos 2 semanas antes de la firma del consentimiento; d.El tratamiento de la metástasis cerebral puede incluir radioterapia del cerebro entero, radiocirugía (Gamma Knife®, acelerador lineal de partículas o equivalente) o combinación de ambas, según lo considere adecuado el médico responsable del tratamiento. Todos los tratamientos de la metástasis cerebral deben haberse finalizado al menos 14 días antes del día 0 del ciclo 1. 11.Tiene funciones orgánicas adecuadas según lo siguiente: a.Reserva de médula ósea: i.Recuento leucocitos ≥3 × 103/µl; ii.Recuento absoluto neutrófilos (segmentados y cayados) ≥1,5 × 103/µl; iii.Recuento plaquetas ≥100 × 103/µl; iv.Hemoglobina ≥9,0 g/dl con un mínimo de 2 semanas sin transfusiones antes del día 0 del ciclo 1. b.Hepática: i.Bilirrubina total ≤1,5 × límite superior de normalidad (LSN); salvo que la elevación se deba al síndrome de Gilbert con elevaciones transitorias de bilirrubina indirecta; ii.Fosfatasa alcalina, alanina transaminasa y/o aspartato transaminasa ≤3 × LSN. Concentraciones significativas alanina transaminasa o aspartato transaminasa deberán analizarse más a fondo para detectar posible hepatitis vírica. (Nota: Se permite una elevación aislada de fosfatasa alcalina por encima de 3 x LSN debida a metástasis ósea). c.Renal: i.Aclaramiento de creatinina calculado ≥45 ml/min, basado la fórmula original de Cockcroft y Gault en función del peso (Cockcroft and Gault 1976; apartado 12.4 [Anexo D]); ii. Cociente proteínas/creatinina en orina ≤1. Un paciente con cociente proteínas/creatinina >1 podrá inscribirse si presenta ≤2 g de proteínas en orina de 24h. 12.Si se encuentran en edad fértil, los pacientes y sus parejas deben utilizar métodos anticonceptivos durante todo el estudio y durante los 6 meses posteriores a la interrupción del estudio. Un paciente en edad fértil debe estar dispuesto a utilizar 2 métodos anticonceptivos de doble barrera distintos, de eficacia elevada, o la abstinencia sexual durante todo el estudio. |
|
E.4 | Principal exclusion criteria |
1. Is pregnant or breast-feeding. 2. Has documented histology/cytology confirming any of the following: a. Squamous non-small cell lung cancer. (Note: In the event of mixed tumor histology/cytology or predominant cell type other than non-squamous, eligibility will be determined based on the predominant cell type, which must be non-squamous.) b. A patient with any small cell type or large cell neuroendocrine histology. 3. Has a recent (within 6 months prior to Day 0 of Cycle 1) cardiac condition as defined by the New York Heart Association Class II, III, or IV (AHA 1994). 4. Has a recent (within 6 months prior to Day 0 of Cycle 1) history of a significant vascular event (such as aortic aneurysm requiring surgical repair or a recent peripheral arterial thrombosis) and/or history of significant and unstable vascular disease. 5. Has a history of stroke or transient ischemic attack within 6 months prior to Day 0 of Cycle 1, or has a long-term history of more than one of the following vascular thromboembolic events: a. Cerebrovascular accidents b. Transient ischemic attacks c. Myocardial infarctions d. Venous thromboembolic reactions, including pulmonary embolism 6. Is receiving anticoagulant therapy that: a. Is not considered ‘stable’, defined as dosage not maintained for at least 3 months prior to Day 0 of Cycle 1. b. Is not within the targeted international normalized ratio at the time of consent signing. 7. Has a current diagnosis, history, or risk of hemorrhage in the central nervous system (CNS), including the following: a. Patient with CNS metastasis treated by neurosurgical resection or brain biopsy performed within 8 weeks prior to Day 0 of Cycle 1. b. Patient should be off corticosteroids for at least 1 week (7 days) at the time of the post-treatment (for CNS metastasis) brain CT/MRI. 8. Has any prior history of hypertensive crisis and/or hypertensive encephalopathy, or has a current diagnosis or recent history of inadequately controlled hypertension (defined as systolic blood pressure >150 mm Hg and/or diastolic >100 mm Hg, while on antihypertensive medications). 9. Has a recent history of any of the following: a. A major surgical procedure, open biopsy, open pleurodesis, or significant traumatic injury within 28 days prior to Day 0 of Cycle 1. b. Documented history of conditions that may need surgery during the study or within 6 months of signing informed consent. c. Has had either a core biopsy or other minor surgical procedure within 7 days prior to Day 0 of Cycle 1. (Note: Placement of a vascular access device, or a closed pleurodesis, thoracentesis, or mediastinoscopy are allowed). 10. Has a history of any of the following: a. Hemoptysis (approximately >2.5 mL or a half teaspoon) within 3 months prior to Day 0 of Cycle 1. b. A thoracic, central, mediastinal tumor location in contact with major vessels c. A cavitated lung tumor. 11. Has a history of gastrointestinal fistula, perforation, or abscess. 12. Has a current diagnosis or history of a nonhealing wound, active ulcer, or untreated bone fracture. 13. Has prior history of another active malignancy within the last 5 years, other than adequately treated superficial basal cell, superficial/skin squamous cell carcinoma, or carcinomas in situ. 14. Has a known hypersensitivity to any component of carboplatin, paclitaxel, bevacizumab, Chinese hamster ovary cell products, or other recombinant human or humanized antibodies. 15. Has received treatment with any other investigational drug, within the last 30 days or at least 5 half-lives (if available), whichever is longer, should have elapsed prior to Day 0 of Cycle 1. 16. Has previously received treatment with the following: a. Paclitaxel. b. Bevacizumab (Note: Prior intravitreal administration of bevacizumab does not preclude study participation). c. Anthracycline. (Note: May be allowed on a case by case basis after consulting with the medical monitor to rule out an increased risk of cardiac failure). 17. Has documented or known current alcohol/drug abuse that precludes his/her ability to adhere to the protocol. 18. Has any of the following concomitant treatments or conditions: a. Concomitant vaccination that contains an attenuated virus, for instance Yellow Fever vaccine. b. Has a known history of active or latent tuberculosis. c. Has a concomitant systemic disorder (e.g., active infection including known human immunodeficiency virus, viral hepatitis B or C) that, in the opinion of the principal investigator (PI; or designee), would compromise the patient's safety (for instance potential drug interactions, or ability to adhere to the protocol). d. Has any other concomitant condition that precludes the participation in the study through increased risk to the patient and/or potential to impact the PI’s (or designee’s) ability to administer this protocol. |
1.Está embarazada o periodo lactancia; 2.Tiene histología/citología documentada que confirma cualquiera: a.Cáncer de pulmón de células no pequeñas y escamosas. (Nota: En caso de histología/citología tumoral mixta o tipo celular predominante distinto al no escamoso, la idoneidad se determinará en función del tipo celular predominante, que debe ser no escamoso). b.Un paciente con cualquier tipo de células pequeñas o histología neuroendocrina de células grandes. 3.Tiene afección cardíaca reciente (6 meses anteriores día 0 ciclo 1), definida como clase II, III o IV según New York Heart Association (AHA 1994). 4.Tiene antecedentes recientes (6 meses anteriores día 0 ciclo 1) acontecimiento vascular significativo (ej., aneurisma aórtico requiere cirugía de reparación o trombosis arterial periférica reciente) y/o antecedentes enfermedad vascular inestable e importante. 5.Tiene antecedentes accidente cerebrovascular o accidente isquémico transitorio 6 meses anteriores día 0 ciclo 1, o tiene historial a largo plazo de más de 1 de los siguientes acontec. tromboembólicos vasculares: a.Accidente cerebrovascular; b.Accidente isquémico transitorio; c.Infarto miocardio; d.Reacción tromboembólica venosa, incluida embolia pulmonar 6.Está recibiendo tratamiento anticoagulante que: a.No se considera “estable”, definido como posología que no se mantiene durante al menos 3 meses antes día 0 ciclo 1; b.No está dentro del índice internacional normalizado objetivo en el momento de la firma del consentimiento. 7.Tiene diagnóstico actual, antecedentes o riesgo hemorragia en sistema nervioso central (SNC), incluidos: a.Pacientes con metástasis del SNC tratada mediante resección neuroquirúrgica o biopsia cerebral realizada en 8 semanas anteriores día 0 ciclo 1;b.El paciente debe estar sin corticoesteroides durante al menos 1 semana (7 días) en el momento de TAC/RM cerebral postratamiento (para metástasis del SNC). 8.Tiene antecedentes crisis hipertensiva y/o encefalopatía hipertensiva, o tiene diagnóstico actual o antecedentes recientes de hipertensión mal controlada (definida como tensión arterial sistólica >150 mmHg y/o diastólica >100 mmHg, mientras toma medicamentos antihipertensivos). 9.Tiene antecedentes recientes de cualquiera:a.Un procedimiento quirúrgico mayor, biopsia abierta, pleurodesis abierta o traumatismo importante en 28 días previos día 0 ciclo 1; b.Historial docum de afecciones que podrían requerir cirugía durante el estudio o en 6 meses anteriores a la firma del consentimiento;c. Le han realizado biopsia con aguja gruesa u otro procedimiento quirúrgico menor en 7 días anteriores al día 0 del ciclo 1. (Nota: Se permite colocación dispositivo acceso vascular, o pleurodesis cerrada, toracocentesis o mediastinoscopia). 10.Tiene antecedentes de cualquiera: a.Hemoptisis (aproximadamente >2,5 ml ) en 3 meses anteriores al día 0 del ciclo 1; b.Una ubicación torácica, central o mediastínica del tumor en contacto con vasos importantes; c.Tumor pulmonar cavitado. 11.Tiene antecedentes fístula, perforación o absceso gastrointestinales. 12.Tiene diagnóstico actual o antecedentes de herida que no cicatriza, úlcera activa o fractura ósea sin tratar. 13. Tiene antecedentes otra neoplasia maligna activa en últimos 5 años, distinta a carcinoma basocelular superficial, escamoso superficial/cutáneo o carcinoma in situ, adecuadamente tratados. 14. Tiene hipersensibilidad conocida a cualquier componente del carboplatino, paclitaxel, bevacizumab, productos de células ováricas de hámster chino u otros anticuerpos recombinantes humanos o humanizados. 15. Ha recibido tratamiento con otro fármaco en invest. en los últimos 30 días o deben haber transcurrido al menos 5 semividas (si se dispone del dato) antes día 0 ciclo 1, lo que sea más largo. 16. Ha recibido tratamiento previo con: a. Paclitaxel; b.Bevacizumab. (Nota: La administración intravítrea previa de bevacizumab no impide la participación en el estudio); c. Antraciclina. (Nota: Podrá permitirse en función de cada caso particular tras consultarlo con el supervisor médico para descartar riesgo alto de insuficiencia cardíaca). 17.Presenta consumo excesivo actual documentado o conocido de alcohol/drogas que imposibilita su cumplimiento del protocolo. 18.Presenta cualquiera de siguientes tratamientos o afecciones concomitantes: a.Vacuna concomitante que contiene virus atenuado, por ej., vacuna fiebre amarilla; b.Tiene antecedentes conocidos tuberculosis activa o latente; c.Tiene trastorno generalizado concomitante (p. ej., infección activa, incluida virus de inmunodeficiencia humana, hepatitis vírica B o C) que, en opinión del IP podría poner en peligro la seguridad del paciente (por ej., posibles interacciones farmacológicas, o la capacidad de cumplir el protocolo); d.Tiene otra afección concomitante que impide la participación en el estudio debido a mayor riesgo para el paciente y/o a la posibilidad de influir en capacidad del IP para poder aplicar este protocolo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the ORR |
El criterio de valoración principal de la eficacia será la TRG |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
During first 18 weeks |
Durante las primeras 18 semanas |
|
E.5.2 | Secondary end point(s) |
Efficacy Endpoints: · DCR (CR, PR, or stable disease) · PFS · OS · DR · TP PK Endpoints: PopPK measures of exposure of MYL-1402O and the reference product Avastin (e.g., AUC, Cmax, Cmin, CL, Vc, and the terminal elimination half-life). Safety Endpoints: · Incidence, nature, and severity of AEs including adverse drug reactions graded according to CTCAE. · Detection of antibodies to bevacizumab. |
Criterios de eficacia: · TCE (CR, PR, o enfermedad estable) · SSP · SG · DR · TP Criterios PC: Las medidas FCpob de exposición al MYL_1402O y el producto de referencia Avastin (por ejemplo, ABC, Cmax, Cmin, aclaramiento, Vc y semivida terminal de eliminación) Criterios seguridad: - Relacion de causalidad, naturaleza e intensidad de los AA incluidas las reacciones adversas al medicamento clasificadas según los CTCAE - Detección de anticuerpos contra bevacizumab |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints will be assessed during the entire duration of the study in line with the protocol schedule of events. |
Los criterios de valoración serán evaluados durante toda la duración del ensayo en linea con el calendario de pruebas. |
|
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 | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Belarus |
Bosnia and Herzegovina |
Brazil |
Bulgaria |
Croatia |
Georgia |
Hungary |
India |
Indonesia |
Italy |
Korea, Republic of |
Malaysia |
Mexico |
Poland |
Romania |
Russian Federation |
Spain |
Taiwan |
Turkey |
Ukraine |
Vietnam |
|
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
|
The end of study will occur when any of the following conditions are first met: 15 months after randomization of the last patient, 250 death events recorded, all patients have discontinued the study, or administrative closing of study. |
El final de estudio se considerara cuando cualquiera de las siguientes condiciones ocurra primero: 15 meses despues de la aleatorización del ultimo paciente, se hayan registrado 250 muertes, todos los pacientes hayan sido discontinuados del estudio o se haya producido el cierre administrativo del estudio. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |