E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
polycystic kidney disease |
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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 | 10011771 |
E.1.2 | Term | Cystic kidney disease |
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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 this trial is to demonstrate that everolimus (Certican®) has superior efficacy compared with placebo in reducing the mean total kidney volume from baseline to 24 months of treatment in patients with ADPKD. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this trial are: • To assess changes from baseline at Month 24 in mean cyst and parenchyma volumes • To assess changes in renal function between baseline and Month 24 as assessed by calculated GFR (MDRD formula), serum creatinine, and proteinuria • To assess incidence of end-stage renal disease (ESRD), defined by the requirement for renal replacement therapy • To assess changes from baseline at Month 24 in blood pressure • To assess the overall survival • To assess safety and tolerability of the study drug |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females, aged 18 – 65 years 2. Clinical diagnosis of autosomal dominant polycystic kidney disease (ADPKD), (Appendix 6) 3. CKD stage II/III, i.e. calculated GFR (MDRD formula) (ml/min/1.73 m²) has to be 30 - 89 or CKD I, i.e. calculated GFR (MDRD formula) (ml/min/1.73 m²) is ≥ 90 and a kidney volume (estimated by ultrasound) > 1000 mL 4. Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at baseline, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility (see Section 8.2) 5. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained
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E.4 | Principal exclusion criteria |
1. CKD I (a calculated GFR ≥ 90 mL/min/1.73m2) and a kidney volume (estimated by ultrasound) of ≤ 1000 ml 2. Patients with CKD stage IV (a calculated GFR < 30 mL/min/1.73m2) 3. Patients with a history of subarachnoid bleeding 4. Patients with a history of serious infections 5. Patients with life-threatening urinary tract or cyst infection in the past 6. Patients who have received any investigational drug within four weeks prior to baseline 7. Patients who have been treated with any non-protocol immunosuppressive drug or treatment within one month prior to baseline 8. Patients with any severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment, or any known hypersensitivity to Certican®, other drugs similar to Certican® (e.g., macrolides), or other components of the formulations (e.g. lactose) 9. Patients with any surgical or medical condition, which in the opinion of the investigator, preludes enrollment in the trial 10. Evidence of severe liver disease (incl. abnormal liver enzyme profile, i.e. AST, ALT, AP or total bilirubin > 3 times UNL) 11. Patients who are HIV positive or Hepatitis B surface antigen positive or who are known to have chronic active Hepatitis C. Laboratory results obtained within 6 months prior to baseline are acceptable 12. Patients with symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator, who are unlikely to comply with the study requirements, or who are unable to give informed consent 13. Patients with unresolved history or evidence of drug or alcohol abuse 14. Presence of severe hypercholesterolemia (≥ 350 mg/dL, 9.1 mmoL/L), or hypertriglyceridemia (≥ 500 mg/dL, 5.6 mmoL/L), if hyperlipidemia is not sufficiently controlled by fluvastatines 15. Patients with white blood cell count count ≤ 4,000/mm³, or platelet count ≤ 100,000/mm³ 16. Patients with a history of malignancy during the last five years, except for successfully treated localized squamous or basal cell carcinoma of the skin 17. Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation (low-dose aspirin treatment is allowed) 18. Patients with abnormal physical or laboratory findings of clinical significance within two weeks prior to randomization which at the investigators discretion would interfere with the objectives of the study 19. Females of childbearing potential who are planning to become pregnant, who are pregnant or breast feading, and/or who are unwilling to use effective means of contraception during the study period and until six weeks after discontinuation of study medication. 20. Patients with a contraindication against MRI
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable for assessment of total kidney volume measured by MRI is the change from baseline in total renal volume [ml/year] at Month 24. |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 17 |
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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |