E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stable, adult kidney transplant recipients (at least 12 months post transplant) who are currently treated with cyclosporine and who meet the Inclusion and Exclusion Criteria will be enrolled. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023438 |
E.1.2 | Term | Kidney transplant |
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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 |
Primary objective is to assess the changes in kidney function in kidney transplant subjects converted from a CyA-based immunosuppressive regimen to a tacrolimus modified release, FK506E (MR4), based immunosuppressive regimen. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the safety and the efficacy of a MR4-based immunosuppressive regimen in kidney transplant subjects converted from a CyA-based immunosuppressive regimen experiencing CyA-related side effects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years. 2. Kidney transplant at least 12 months prior to enrollment. 3. Received a CyA-based immunosuppressive regimen since last transplantation. The dose of CyA has remained unchanged during the last four weeks prior to enrollment. 4. Immunosuppressive regimen (combination of medications) remained unchanged for a minimum of four weeks prior to enrollment. 5. Experienced at least one of the following CyA-related adverse events at enrollment: a) Gingival hyperplasia where, in the opinion of the investigator, therapeutical intervention is required. b) Hypertrichosis/hirsutism where, in the opinion of the investigator, therapeutical intervention is required. c) Arterial hypertension (with the exception of known pre-transplant malignant nephrosclerosis) stages I-III (systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90mmHg) despite treatment with at least one anti-hypertensive medication. The anti-hypertensive medication(s) has been prescribed at least 4 weeks prior to enrollment. d) Hyperlipidemia defined as total cholesterol higher than 220 mg/dl despite treatment with lipid-lowering medication(s) requires therapeutical intervention. The lipid-lowering medication(s) has been prescribed at least four weeks prior to enrollment. 6. Serum creatinine < 200 µmol/l (< 2.3 mg/dl) at enrollment. 7. Female subject of childbearing potential must have a negative serum pregnancy test at enrollment and must agree to maintain effective birth control during the study. 8. Capable of understanding the purpose and risks of the study, has been fully informed and has given written informed consent (signed Informed Consent has been obtained). 9. Clinically stable in the opinion of the investigator. |
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E.4 | Principal exclusion criteria |
1. Previously received an organ transplant other than a kidney. 2. Acute rejection episode within 12 weeks prior to enrollment, or an acute rejection episode within the 24 weeks prior to enrollment 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 had been treated successfully. 4. Known to have FSGS or MPGN Type II as an underlying disease. 5. Proteinuria > 2 g / 24 hrs. 6. “Creeping creatinine” (defined as an increase of 20% within the 6 months prior to enrollment and at Baseline). 7. 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. 8. Liver cirrhosis. 9. Pregnant woman or breast-feeding mother. 10. HIV positive. 11. Known allergy or intolerance to tacrolimus, macrolide antibiotics, steroids, additional concomitant immunosuppressive medication or to the excipients of the study medication. 12. Any unstable medical condition that could interfere with the study objectives in the opinion of the investigator. 13. Receiving prohibited concomitant therapy, or received prohibited concomitant therapy within 28 days prior to enrollment. 14. Currently participating in another clinical trial, and/or has taken an investigational drug within 28 days prior to enrollment. 15. Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator. 16. Unlikely to comply with the visits scheduled in the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in creatinine clearance, calculated according to Cockcroft and Gault formula, between Baseline (Day 1) and week 24 (End of Study) for each specific CyA-related side-effect group (hypertrichosis/hirsutism, gingival hyperplasia, hyperlipidemia, arterial hypertension). |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 | Information not present in EudraCT |
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 |
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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
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 0 |