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 |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
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 goal of this study is to investigate if the intra-patient variability in tacrolimus pharmacokinetics is reduced by switching patients from maintenance tacrolimus treatment with tacrolimus-Prograft to either Advagraf or to Envarsus.
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E.2.2 | Secondary objectives of the trial |
Secondary goals are:
1. Study the correlation between CYP3A5 genotype and intra-patient variability of tacrolimus clearance.
2. Study the impact of switching from tacrolimus-Prograft to either of the once daily formulations on patient satisfaction and quality of life.
3. Study the influence of age and gender on intra-patient variability.
4. Study the preference of patients for choice of formulation for continuation after study closure.
5. Study the effect of switching to either of the once daily formulations on incidence of acute rejection, on renal function and on adverse events.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria. Subjects are eligible for the study if all of the following apply:
1. Age ≥ 18 years.
2. Kidney transplant at least 12 months prior to enrollment and clinically stable in the opinion of the investigator.
3. Prograft® based immunosuppressive regimen.
4. Prograft® dose unchanged for a minimum of 12 weeks prior to enrollment.
5. Immunosuppressive regimen (combination of medications) remained unchanged for a minimum of 12 weeks prior to enrollment.
6. Female subject of childbearing potential must agree to practice effective birth control during the study.
7. Capable of understanding the purpose and risks of the study, fully informed and given written informed consent (signed Informed Consent Form has been obtained).
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E.4 | Principal exclusion criteria |
Exclusion Criteria. Subjects will be excluded from participation if any of the following apply:
1. Previously received an organ transplant other than a kidney.
2. Acute rejection episode within 6 months prior to enrolment, or an acute rejection episode within the 12 months prior to enrolment that required anti-lymphocyte antibody therapy.
3. Diagnosis of new-onset malignancy after transplantation, with the exception of basocellular or squamous cell carcinoma of the skin, which have been treated successfully.
4. Known allergy to the study drug or any of its components.
5. Any unstable medical condition that could interfere with the study objectives in the opinion of the investigator.
6. Any form of substance abuse, psychiatric disorder or condition, which, in the opinion of the investigator, may complicate communication with the investigator.
7. Active participation in another clinical trial.
8. Breast-feeding mother.
10. HIV positive.
11. Unlikely to comply with the visits scheduled in the protocol.
12. Proteinuria > 2 g / 24 hrs.
13. GFR estimated according to MDRD to be < 20 mL/min/1.73m2.
14. Patient with deteriorating renal function (defined as an increase of creatinine of >20 % over the 6 months prior to enrolment).
15. 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.
16. Patient is known to have liver cirrhosis.
17. Previous treatment with Envarsus or Advagraf.
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E.5 End points |
E.5.1 | Primary end point(s) |
The intra-patient variability of the pharmacokinetics of all three formulations, |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. The correlation between CYP3A5 genotype and intra-patient variability of tacrolimus clearance.
2. The impact of switching from tacrolimus-Prograft to either of the once daily formulations on patient satisfaction and quality of life.
3. The preference of patients for choice of formulation for continuation after study closure.
5. The effect of switching to either of the once daily formulations on incidence of acute rejection, on renal function and on adverse events.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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) | 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 | 2 |
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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LVLS |
laatste visite van laatste patient |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |