E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary hyperparathyroidism (SHPT) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020708 |
E.1.2 | Term | Hyperparathyroidism secondary |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020708 |
E.1.2 | Term | Hyperparathyroidism secondary |
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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 superiority of paricalcitol as compared to cinacalcet with supplemental low dose vitamin D therapy, as assessed by the proportion of haemodialysis subjects that achieve a mean iPTH value between 150 to 300 pg/mL during Weeks 21 to 28. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the following: 1. The proportion of subjects achieving at least 30% reduction from baseline in iPTH as assessed by the mean iPTH obtained in Weeks 21 to 28. 2. The proportion of subjects achieving at least 50% reduction from baseline in iPTH as assessed by the mean iPTH obtained in Weeks 21 to 28. 3. The change from baseline in iPTH, calcium and calcium-phosphorus product as assessed by the mean values obtained in Weeks 21 to 28. 4. The proportion of subjects with calcium < 8.4 mg/dL (2.09 mmol/L) between treatment groups as assessed by the mean calcium obtained in Weeks 21 to 28. 5. The proportion of subjects with calcium > 10.5 mg/dL (2.61 mmol/L) as assessed by the mean calcium obtained in Weeks 21 to 28. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A patient will be eligible for study participation if he/she meets the following criteria:
1. Male or female patients ≥ 18 years old. 2. Patient has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the patient has had the opportunity to ask questions. The informed consent must be signed prior to the conduct of any study specific Screening procedures or withholding any medications. 3.Patient is diagnosed with Stage 5 CKD and has been receiving IV or oral vitamin D receptor activators (VDRAs) or cinacalcet during the 8 weeks prior to the Screening Period or naïve patients that have not received VDRA or cinacalcet within 8 weeks of Screening. 4. Patient is on maintenance HD (hemodialysis) TIW for at least 3 months prior to screening and is expected to remain on HD for the duration of the study. 5. For entry into the Pre-Treatment Washout Period (for patients that are not naïve to VDRAs or cinacalcet), the patient must have Screening laboratory values of: ● iPTH level 130 to 700 pg/mL inclusive ● Serum Total Alkaline Phosphatase level ≥ 40 U/L ● Calcium level ≤ 10.0 mg/dL (2.49 mmol/L) ● CaxP ≤ 75 mg2/dL2 (US) and ≤ 70 mg2/dL2 (ex-US) For entry into Treatment Period (for patients that have completed the washout or that are naïve to VDRAs or cinacalcet), the patient must meet the following laboratory criteria prior to randomization: ● iPTH level 300−800 pg/mL inclusive ● Calcium level of 8.4 to 10.0 mg/dL inclusive (2.09 to 2.49 mmol/L) ● Phosphorus For entry into Treatment Period (for patients that have completed the washout or that are naïve to VDRAs or cinacalcet), the patient must meet the following laboratory criteria prior to randomization: ● iPTH level 300−800 pg/mL inclusive ● Calcium level of 8.4 to 10.0 mg/dL inclusive (2.09 to 2.49 mmol/L) ● Phosphorus For entry into Treatment Period (for patients that have completed the washout or that are naïve to VDRAs or cinacalcet), the patient must meet the following laboratory criteria prior to randomization: ● iPTH level 300−800 pg/mL inclusive ● Calcium level of 8.4 to 10.0 mg/dL inclusive (2.09 to 2.49 mmol/L) ● Phosphorus ≤ 6.5 mg/dL (2.09 mmol/L) 6. If female, patient is not breastfeeding. 7. If female, patient must have a negative serum pregnancy test prior to the Treatment Period. 8. If female, patient is either not of childbearing potential, defined as postmenopausal for at least 1 year, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or is of childbearing potential and practicing one of the following methods of birth control: ● Maintains a monogamous relationship with a vasectomized partner. ● Double barrier method (any two of the following: condoms, contraceptive sponge, diaphragm, vaginal ring with spermicidal jellies or creams or intrauterine device [IUD]). ● Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to and during study drug administration. ● Total abstinence from sexual intercourse during the study (minimum one complete menstrual cycle prior to study start). |
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E.4 | Principal exclusion criteria |
A patient will be excluded from the study if he/she meets any of the following criteria:
1.Patient has a history of an allergic reaction or significant sensitivity to drugs similar to the study drugs (paricalcitol, cinacalcet, doxercalciferol [US sites], or alfacalcidol [Ex US sites, including Russia]). 2.Patient is expected to need more than 2.0 grams of oral elemental calcium per day as total intake, which includes > 1.6 grams per day of elemental calcium as the phosphate binder. 3. Patient has a history of parathyroidectomy. 4. Patient has chronic gastrointestinal (GI) disease, which, in the opinion of the investigator, may result in clinically significant gastrointestinal malabsorption. 5.Patient has a current malignancy (with the exception of basal or squamous cell carcinoma of the skin), or clinically significant liver disease, defined as ≥ 3 x the upper limit of normal (ULN) for serum glutamic-oxaloacetic transaminase (SGOT/AST), serum glutamic pyruvic (SGPT/ALT) and total bilirubin as determined by medical history. 6. Patient has a history of drug or alcohol abuse that, in the opinion of the investigator, is thought to impact the patient's participation in the study. 7. Patient has evidence of poor compliance with diet, medication or HD that may interfere, in the opinion of the investigator, with adherence to the protocol. 8.Use of known inhibitors (i.e., ketoconazole) or inducers (i.e., carbamazepine) of cytochrome P450 (including grapefruit and/or grapefruit juice) 3A (CYP3A) or drugs metabolized by cytochrome P450 2D6 (CYP2D6) (e.g., flecainide, vinblastine, thioridazine and most tricyclic antidepressants) within 2 weeks prior to study drug administration. Commonly used beta blockers such as metoprolol and carvedilol are allowed but are metabolized by CYP2D6, thus, an adjustment to a lower dose may be required. 9. Patient has participated in any investigational study or received any investigational drug within 4 weeks prior to the Treatment Period. 10. After entry into the Pre-Treatment Washout Period, patient is taking calcitonin, maintenance IV or oral glucocorticoids (> 5 mg per day of prednisone or equivalent), bisphosphonates, immunosuppressants or other drugs that may affect calcium or bone metabolism, other than calcium and non-calcium containing phosphate binders or females on stable estrogen and/or progestin therapy (same dose and product for 3 months prior to study drug administration). 11. Patient is known to be HIV positive. 12. For any reason, subject is considered by the investigator to be an unsuitable candidate to receive any of the study medications or is put at risk by study procedures. 13. Patient has any of the known contraindications of cinacalcet. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the proportion of subjects that achieve a mean iPTH value between 150 to 300 pg/mL during Weeks 21 to 28 of the Treatment Period. |
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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 | 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 | 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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 | 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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The date of the last subject's visit or follow-up (last visit + 30 days), whichever is longer. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |