E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis of transplant rejection in adult kidney allograft recipients. |
Profilaxis del rechazo del trasplante en receptores de un injerto renal |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of rejection of transplanted kidney in adults. |
Prevención del rechazo en adultos que reciben un trasplante renal. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023439 |
E.1.2 | Term | Kidney transplant rejection |
E.1.2 | System Organ Class | 10021428 - Immune system 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 |
The primary objective of the study is to assess if Advagraf® pharmacokinetic parameters measured prior to transplantation can predict the dose required after transplantation to achieve target trough levels of 10 ng/mL in individual patients. |
El objetivo principal de este estudio es evaluar si los parámetros farmacocinéticos de Advagraf® medidos antes del trasplante pueden predecir la dosis postrasplante necesaria para alcanzar las concentraciones diana mínimas de 10 ng/mL en cada paciente. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to evaluate the influence of pharmacogenetics on early post-transplant exposure to tacrolimus. |
El objetivo secundario del estudio es evaluar la influencia de la farmacogenética en la exposición a tacrolimus en la fase inicial postrasplante. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject is eligible for the study if all of the following apply: 1. Aged ? 18 years and undergoing primary kidney allograft transplantation. 2. Receiving a kidney transplant from a deceased donor with compatible ABO blood type. 3. Female subject of childbearing potential has a negative serum or urine pregnancy test at enrollment. 4. Female and male subjects agree to maintain highly effective birth control during the study and for 90 days after end of study participation. 5. Capable of understanding the purpose and risks of the study, fully informed and having given written informed consent (signed Informed Consent has been obtained). |
1. Pacientes de edad ?18 años que vayan a recibir un trasplante de aloinjerto renal primario. 2. Pacientes que vayan a recibir un trasplante renal de un donante fallecido con un grupo ABO compatible. 3. Las mujeres en edad fértil deben tener una prueba de embarazo sérica o urinaria negativa en el momento de la inclusión. 4. Los pacientes (tanto hombres como mujeres) deberán utilizar un método control de la natalidad muy eficaz durante el estudio y durante los 90 días siguientes a la finalización de su participación en el estudio. 5. Pacientes capaces de comprender el objetivo y los riesgos del estudio, ampliamente informados y que den su consentimiento informado por escrito (es necesario tener el formulario de consentimiento informado firmado). |
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E.4 | Principal exclusion criteria |
Subject will be excluded from participation if any of the following apply: 1. Receiving a multi-organ transplant or has previously received an organ transplant. 2. Significant uncontrolled diabetes or liver disease, defined as having continuously elevated SGPT/ ALT and/ or SGOT/ AST and/ or total bilirubin levels ? 2 times the upper value of the normal range of the investigational site. 3. Requiring initial sequential or parallel therapy with immunosuppressive antibody preparation(s). 4. Requiring systemic immunosuppressive medication for any indication other than transplantation. 5. Significant, uncontrolled concomitant infections and/ or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer. 6. Pregnant woman or breast-feeding mother. 7. Subject or donor known to be HIV or HCV or HBV positive. 8. Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids or MMF. 9. Previous exposure to Tacrolimus or requirement for multiple pre-operative doses of Advagraf®. 10. Currently participating in another clinical trial, and/ or has taken an investigational drug within 28 days prior to enrollment. 11. Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the Investigator, may complicate communication with the Investigator. 12. Unlikely to comply with the visits scheduled in the protocol. 13. Subject is taking or requiring to be treated with medication or substances known to interfere with tacrolimus metabolism 14. Any condition which, in the investigator?s opinion, makes the subject unsuitable for study participation. |
1. Pacientes que vayan a recibir un trasplante multiorgánico o que hayan recibido previamente un trasplante de órgano. 2. Diabetes no controlada o enfermedad hepática significativa, definida por niveles de GPT/ALT, GOT/AST o bilirrubina total ? 2 veces el límite superior de la normalidad en el centro de investigación. 3. Pacientes que necesiten iniciar una terapia secuencial o paralela con preparados de anticuerpos inmunosupresores. 4. Pacientes que necesiten medicación inmunosupresora sistémica para cualquier otra indicación diferente del trasplante. 5. Pacientes que presenten infecciones concomitantes significativas no controladas o diarrea grave, vómitos, malabsorción activa del tracto gastrointestinal superior o úlcera péptica activa. 6. Mujeres embarazadas o madres lactantes. 7. Receptor o donante positivos para VIH, VHC o VHB. 8. Intolerancia o alergia conocida a tacrolimus, antibióticos macrólidos, corticosteroides o MMF. 9. Exposición previa a tacrolimus o necesidad de recibir múltiples dosis preoperatorias de Advagraf®. 10. Pacientes que estén participando actualmente en otro ensayo clínico o hayan recibido un fármaco en investigación en los 28 días previos a la inclusión. 11. Cualquier tipo de abuso de sustancias, trastorno psiquiátrico u otro problema que, en opinión del investigador, pudiera complicar la comunicación con el investigador. 12. Poca probabilidad de que el paciente acuda a las visitas programadas en el protocolo. 13. El paciente está recibiendo o necesita recibir tratamiento con medicamentos o sustancias de las que se sabe que interfieren con el metabolismo de tacrolimus. 14. Cualquier enfermedad que, en opinión del investigador, haga que el paciente no sea apto para participar en el estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
? The primary variable is dose of tacrolimus required to achieve a trough level of 10 ng/mL on Day 3 after transplantation. |
La variable principal es la dosis de tacrolimus necesaria para alcanzar un nivel mínimo de 10 ng/mL el día 3 postrasplante. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 3 after transplantation. |
Dia 3 después del trasplante |
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E.5.2 | Secondary end point(s) |
? Dose-normalised trough concentration of tacrolimus on Day 7 and Day 14 after transplantation ? Tacrolimus trough concentrations on Day 7 and Day 14 after transplantation ? Tacrolimus concentrations 1, 2 and 3 hours (C1, C2, C3) after pre-transplant test dose ? AUC0-3 following the test dose ? Cmax, tmax following the test dose
? Genetic polymorphisms in CYP3A4/5 and ABCB1 genes
? Delayed graft function ? Biopsy Confirmed Acute Rejection (BCAR) ? Incidence of Adverse Events (AEs) ? Laboratory parameters ? Vital signs |
? Concentración mínima de tacrolimus con normalización de la dosis los días 7 y 14 postrasplante ? Concentraciones mínimas de tacrolimus los días 7 y 14 después del trasplante ? Concentraciones de tacrolimus 1, 2 y 3 horas (C1, C2, C3) después de la dosis de prueba pretrasplante ? AUC0?3 tras la dosis de prueba ? Cmáx y tmáx tras la dosis de prueba |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day -1 (pre-operative): 1, 2 and 3 hours after pre-transplant test dose Day 1, Day 3, Day 7 and Day 14 (post-operative) |
Dia -1 ( pre-operativa): 1, 2 y 3 horas después de la dosis de prueba pretrasplante Día 1, Día 3, Día 7 yDía 14 (post-operativa) |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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LVLS |
Último paciente última Visita |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 15 |