E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Patients above 18 years transplanted with a kidney from either a living- or deceased donor |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023438 |
E.1.2 | Term | Kidney transplant |
E.1.2 | System Organ Class | 100000004865 |
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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 investigate the association between microbiome diversity and 12-hour mycophenolate pharmacokinetics |
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E.2.2 | Secondary objectives of the trial |
-association between microbiome diversity and 12-hour Tac PK -effects of MMF treatment on gut microbiome changes in treatment naïve patients and associated MPA 12-hour PK changes. -effects of Tac treatment on gut microbiome changes in treatment naïve patients and associated Tac 12-hour PK changes. -indirect association between microbiome diversity and immunosuppressant molecular pharmacodynamics (PD biomarkers). -compare gut microbiome diversity after kidney transplantation in Norwegian and US patients. -investigate if TTV is a clinical useful “immunometer”, i.e. reflect overall immunosuppression of the recipient. -investigate whether immunosuppressant molecular pharmacodynamics (cytokine responses, intracellular drug and drug target levels and down-stream mediators) can be predictive for rejection and adverse effects. -integrate the updated knowledge on MPA and Tac PK following renal transplantation in a combined population pharmacokinetic model for individualized dosing. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
De novo, standard risk kidney (only) transplant recipients. Patients scheduled to receive tacrolimus and mycophenolate mofetil as part of their immunosuppressive therapy following transplantation (clinical decision not influenced by this study). First kidney transplant only. Adult patients.
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E.4 | Principal exclusion criteria |
Pregnant or lactating female patients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Association between microbiome diversity measures and AUC0-tau and Cmax of mycophenolate and metabolites |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Three to eight weeks and one year after transplantation |
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E.5.2 | Secondary end point(s) |
1. Association between microbiome diversity measures and absolute F, AUC0-tau and Cmax of tacrolimus and metabolites. 2. Changes in microbiome diversity measures and mycophenolate (and metabolite) AUC0-tau, Cmax, Tmax and kel with one week of mycophenolate mofetil treatment. 3. Changes in microbiome diversity measures and tacrolimus (and metabolite) AUC0-tau, Cmax, Tmax and kel with one week of tacrolimus treatment. 4. Association between microbiome diversity measures and immunosuppressant molecular pharmacodynamics (PD markers), indirectly linked through pharmacokinetics. 5. Descriptive comparison of microbiome diversity measures between the two populations. 6. Associations between TTV viral load and immunosuppressive drug systemic exposure, acute rejection episodes, protocol biopsy scores and other opportunistic infections, e.g. CMV and BK DNAemia and incidence of bacterial infections. 7. Diagnostic sensitivity and specificity for immunosuppressant pharmacodynamic biomarkers as predictors for rejection and adverse effects. 8. Relative predictive error (PE%) and root mean squared error (RMSE%) of the developed pharmacokinetic model. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Three to eight weeks and one year after transplantation |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Association study without control but pretransplant invest. randomized to either drug in parallel |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |