- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01292226
A Study of the Correlation Between Pharmacokinetic and Pharmacodynamic Parameters of CellCept (Mycophenolate Mofetil).
8 de abril de 2016 actualizado por: Hoffmann-La Roche
Relationships Between Pharmacokinetic and Pharmacodynamic Strategies for Assessment of the Risks for Acute Rejection and Side Effects of Mycophenolate Mofetil
This study will evaluate the correlation between the pharmacokinetic and pharmacodynamic parameters of CellCept in patients undergoing primary kidney transplantation, in order to assess the impact on clinical outcome and the risks of acute rejection.
All patients will receive oral CellCept, 1g twice daily, and pharmacokinetic and pharmacodynamic parameters will be measured at weeks 2, 4, 12 and 24.
The anticipated time on study treatment is 24 weeks.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
45
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
-
Bari, Italia, 70124
-
Brescia, Italia, 25123
-
Coppito, Italia, 67100
-
Napoli, Italia, 80131
-
Roma, Italia, 00168
-
Torino, Italia, 10126
-
Verona, Italia, 37126
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 65 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Adult patients, 18 to 65 years of age
- Patients undergoing primary kidney transplantation
Exclusion Criteria:
- Recipients of multiple organ transplants
- Prior therapy with CellCept
- Presence or history of malignancies, except for successfully treated basal or squamous cell carcinoma of the skin
- Active peptic ulcer or active serious digestive system disease that may affect the absorption of CellCept
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: Mycophenolate Mofetil Monotherapy
Participants received an initial dose of mycophenolate mofetil (MMF), 1 gram (g), orally (PO), twice per day (BID), within 5 days of transplant for 24 weeks.
Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
|
1 g PO BID for 24 weeks
Otros nombres:
According to manufacturer recommendation
According to manufacturer recommendation
According to manufacturer recommendation
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Percentage of Participants With Acute Rejection
Periodo de tiempo: Day 1, Weeks 2, 4, 12, 24, and 28
|
Diagnosis of acute rejection was suspected in any participant with an increase in serum creatinine greater than or equal to (≥) 25 percent (%).
All suspected acute rejections were confirmed by biopsy.
The start date of acute rejection was identified as the date of biopsy.
|
Day 1, Weeks 2, 4, 12, 24, and 28
|
Time to Rejection
Periodo de tiempo: Day 1, Weeks 2, 4, 12, 24, and 28
|
The mean time, in days, from the date of enrollment to date of biopsy confirming acute rejection.
|
Day 1, Weeks 2, 4, 12, 24, and 28
|
Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR)
Periodo de tiempo: Day 1, Weeks 2, 4, 12, 24, and 28
|
BPAR was defined according to 1997 Banff Criteria as a biopsy Banff grade of IA, IB, IIA, IIB, or III.
Grade IA was defined as significant interstitial infiltration with greater than (>)25% of parenchyma affected, and foci of moderate tubulitis with >4 mononuclear cells per tubular cross section or group of 10 tubular cells.
Grade IB was defined as significant interstitial infiltration with >25% parenchyma affected, and foci of severe tubulitis with >10% mononuclear cells per tubular cross section or group of 10 tubular cells.
Grade IIA was defined as mild to moderate intimal arteritis.
Grade IIB was defined as severe intimal arteritis comprising >25% of the luminal area.
Grade III was defined as transmural arteritis and/or arterial fibrinoid changes and necrosis of medial smooth muscle cells.
|
Day 1, Weeks 2, 4, 12, 24, and 28
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Percentage of Participants With Graft Loss
Periodo de tiempo: Day 1, Weeks 2, 4, 12, 24, and 28
|
An allograft was presumed to be lost if a participant started dialysis and was not able to subsequently be removed from dialysis.
|
Day 1, Weeks 2, 4, 12, 24, and 28
|
Percentage of Participants Surviving
Periodo de tiempo: Day 1, Weeks 2, 4, 12, 24, and 28
|
Day 1, Weeks 2, 4, 12, 24, and 28
|
|
Total Mycophenolate Acid (MPA) by Visit and Timepoint
Periodo de tiempo: Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up Visit), and any unscheduled visits
|
Drug quantification of total MPA (micrograms per milliliter [mcg/mL]) in the plasma was measured at time (T) = 0 minutes (min), 40 mins, and 120 mins.
|
Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up Visit), and any unscheduled visits
|
Free MPA (mcg/mL) by Visit
Periodo de tiempo: Weeks 2, 4, 12, 24, safety follow-up (Week 28), and any unscheduled visits
|
Drug quantification of free MPA in the plasma was measured at T = 0, 40, and 120 mins.
|
Weeks 2, 4, 12, 24, safety follow-up (Week 28), and any unscheduled visits
|
MPA Area Under the Concentration - Time Curve From Time 0 to 12 Hours (AUC0-12) (mcg/mL) by Visit
Periodo de tiempo: Predose and 40 minutes and 2 hours postdose at Weeks 2, 4, 12, and 24, and at the Safety follow-up (Week 28)
|
The AUC0-12 of MPA was estimated on the validated limited sampling strategy, AUC (milligrams multiplied by height over liter [mg.h/L]) = 7.182 + 4.607 multiplied by (*) concentration at 0 minutes (C0)+ 0.998 * the concentration at 40 minutes (C0.67) + 2.149 * the concentration at 120 minutes (C2).
|
Predose and 40 minutes and 2 hours postdose at Weeks 2, 4, 12, and 24, and at the Safety follow-up (Week 28)
|
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
|
IMPDH activity in peripheral blood mononuclear cells (PBMCs) was measured at 2 timepoints per visit, 0 and 120 minutes and presented in enzyme units.
The unit of measure of enzyme activity is "U".
One U is defined as the amount of the enzyme that produces a certain amount of enzymatic activity that is, the amount that catalyzes the conversion of 1 micro mole of substrate per minute under pre-specified conditions (temperature, pH).
|
BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
|
IMPDH Expression I by Visit and Timepoint
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
|
IMPDH I gene expression was measured by real time polymerase chain reaction (QRT-PCR) based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of messenger ribonucleic acid (mRNA) copies per cell (copies/cell).
|
BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
|
IMPDH Expression II by Visit and Timepoint
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
|
IMPDH II gene expression was measured by QRT-PCR based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of mRNA copies/cell.
|
BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
|
Interleukin 8 (IL-8) Expression by Visit and Timepoint
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
|
IL-8 gene expression was measured by QRT-PCR based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of mRNA copies/cell.
|
BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
|
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
|
TNF gene expression was measured by QRT-PCR based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of mRNA copies/cell.
|
BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
|
Percentage of Participants With Infection
Periodo de tiempo: BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)
|
Infections were graded according to the World Health Organization (WHO) worst grade observed.
|
BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)
|
Percentage of Participants With Gastrointestinal Toxicities
Periodo de tiempo: BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-up Visit)
|
Gastrointestinal adverse events (AEs) according to WHO worst grade observed.
|
BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-up Visit)
|
Percentage of Participants With Hematologic Toxicity
Periodo de tiempo: BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)
|
Hematological toxicities graded according to WHO worst grade observed (Grade 1=mild, Grade 2=moderate).
|
BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)
|
Spearman's Rank Correlation Coefficient Between MPA Levels and IMPDH Activity
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between IMPDH I Expression and MPA Levels
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between IMPDH I Expression and Free Fraction
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between IMPDH II Expression and MPA Levels
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between IMPDH II Expression and Free Fraction
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Infection
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Hematologic Toxicity
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Gastrointestinal Toxicity
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Infection
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Hematologic Toxicity
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Gastrointestinal Toxicity
Periodo de tiempo: BL and Weeks 2, 4, 12, and 24
|
The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula.
In case of ties, the averaged ranks were used.
|
BL and Weeks 2, 4, 12, and 24
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de diciembre de 2006
Finalización primaria (Actual)
1 de septiembre de 2008
Finalización del estudio (Actual)
1 de septiembre de 2008
Fechas de registro del estudio
Enviado por primera vez
3 de febrero de 2011
Primero enviado que cumplió con los criterios de control de calidad
8 de febrero de 2011
Publicado por primera vez (Estimar)
9 de febrero de 2011
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
12 de mayo de 2016
Última actualización enviada que cumplió con los criterios de control de calidad
8 de abril de 2016
Última verificación
1 de abril de 2016
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Inhibidores de enzimas
- Agentes antirreumáticos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes dermatológicos
- Agentes antibacterianos
- Antibióticos, Antineoplásicos
- Agentes antifúngicos
- Agentes antituberculosos
- Antibióticos, Antituberculosos
- Inhibidores de calcineurina
- Anticuerpos
- Ácido micofenólico
- Ciclosporina
- Ciclosporinas
Otros números de identificación del estudio
- ML19835
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre mycophenolate mofetil
-
University Hospital Schleswig-HolsteinTerminado
-
Colorado Blood Cancer InstituteDesconocidoEnfermedad de injerto contra huéspedEstados Unidos
-
Asan Medical CenterDesconocidoHEPATITISCorea, república de
-
University of GiessenNovartis; Hoffmann-La Roche; Astellas Pharma Inc; Heidelberg UniversityTerminadoInfecciones por poliomavirusAlemania