E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetic nephropathy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic 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 |
To evaluate the safety and efficacy of paricalcitol capsules on albuminuria reduction in CKD subjects with Type 2 diabetic nephropathy receiving optimal ACEi and/or Angiotensin II-Receptor-Blocker therapy |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC). 2. Male or female subjects equal to or greater than 20 years old. 3. Subject has Type 2 Diabetes Mellitus and has been treated with at least one anti-hyperglycemic medication within the 12 months prior to the Screening Phase. 4. Subject has been receiving a stable dose (i.e., same type and regimen) of ACEi and/or ARB for at least three months prior to the Screening Phase. However, subject may have switched to different brands but at equivalent doses during the three months prior to the Screening Phase. 5. Subject is not expected to begin dialysis for at least six months. 6. If female, subject is not breast feeding or is not pregnant ; or is not of childbearing potential; or is of childbearing potential and practicing a method of birth control. 7. For entry into the Treatment Phase the subject must satisfy the following criteria based on the Screening laboratory values: a. Estimated GFR between 15-75 mL/min/1.73m2 by simplified MDRD formula. b. UACR between 100 and 3000 mg/g (11.3-339 mg/mmol) as determined by the mean of the three first morning void urine specimens obtained within one week. c. Corrected serum calcium level equal to or less than 9.8 mg/dL (2.45 mmol/L). d. iPTH value between 35-500 pg/mL. e. HbA1c equal to or less than 12%. f. Serum albumin > 3.0 g/dL. g. Negative urine pregnancy test for female subjects.
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E.4 | Principal exclusion criteria |
1. Subject has previously been on prescription-based vitamin D therapy within the six months prior to the Screening Phase. 2. Subject has a history of an allergic reaction or significant sensitivity to paricalcitol or to drugs similar to the study drug. 3. Subject has primary glomerulopephritis or secondary nephritis in addition to diabetic nephropathy. 4. Subject has had acute renal failure within 12 weeks of the Screening Phase defined by an acute rise in serum creatinine (of at least 0.5 mg/dL or 44 µmol/L) to more than 4 mg/dL (350 µmol/L). 5. Subject has chronic gastrointestinal disease, which in the Investigator's opinion may cause significant GI malabsorption. 6. Subject has secondary hypertension (i.e., renal artery stenosis, primary aldosteronism or pheochromocytoma). 7. Subject has poorly controlled hypertension (systolic blood pressure equal to or greater than 160 mmHg and or diastolic blood pressure equal to or greater than 100 mmHg). 8. Subject has a history of kidney stones. 9. Subject has a history of drug or alcohol abuse within six months prior to the Screening Phase. 10. Subject has evidence of poor compliance with diet or medication that may interfere, in the Investigator's opinion, with adherence to the protocol. 11. Subject has received any investigational drug within 30 days prior to study drug administration. 12. Subject is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except topical glucocorticoids) or other drugs that may affect calcium or bone metabolism, other than calcium containing phosphate binder or female subjects on stable (same dose and product for three months) estrogen and/or progestin therapy. 13. For any reason, subject is considered by the Investigator to be an unsuitable candidate to receive paricalcitol capsules or is put at risk by study procedures. 14. Subject is known to be HIV positive. 15. Use of known inhibitors (i.e., ketoconazole) or inducers (i.e. carbamazepine) of cytochrome P450 3A (CYP3A) within two weeks prior to study drug administration.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline to the last on-treatment UACR measurement using UACR levels determined from the first morning void urine collections |
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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 | 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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |