E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
secondary hyperparathyroidism in paediatric subjects with chronic kidney disease |
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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 | 10020708 |
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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 determine the efficacy of cinacalcet HCl plus standard therapy for SHPT in paediatric subjects with CKD on dialysis by assessing the response to treatment (e.g., a reduction from baseline >25% in mean intact parathyroid hormone (iPTH) levels with concomitant values for P<6 mg/dL and Ca between 8.4-10.5 mg/dL or Ca x P product <60) after 6 months compared to standard therapy alone intra-subject; AND - To evaluate the overall safety and tolerability of cinacalcet HCl plus standard therapy for SHPT in paediatric patients with CKD on dialysis over 6 months compared to standard therapy alone intra-subject. |
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E.2.2 | Secondary objectives of the trial |
-to determine the efficacy of cinacalcet HCl plus standard therapy in the target population by assessing the response to treatment during the induction period over 6 months, and during the maintenance period over 12 months; - To evaluate the overall safety and tolerability of cinacalcet HCl plus standard therapy in the target population over 18 months; - To evaluate the effects of cinacalcet HCl on bone growth by measuring anthropometric indices (Height-for-Age, Weight-for-Age, Weight-for-Height, Body Mass Index-for-Age) and subject growth velocity over 18 months; - In a subset of adolescent subjects (12-18 yrs), to assess the pharmacokinetics (PK)/pharmacodynamic (PD) profile of cinacalcet HCl and its correlation with iPTH target levels and testosterone level when applicable; - In a subset of children (2-11 yrs), to explore the population clinical pharmacology of cinacalcet HCl. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOCINETICA/FARMACODINAMICA: Versione:1 Data:2009/08/17 Titolo:analisi farmacocinetica Obiettivi:stabilire modalita` di assorbimento, trasformazione ed eliminazione del cinacalcet nei pazienti pediatrici
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E.3 | Principal inclusion criteria |
To be eligible for inclusion into this study, the subjects must fulfill all of the following criteria at study entry: - Parents/guardian written informed consent, and childs assent given before any studyrelated procedure not part of the subjects normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care. - Age > 2 and <18 years; - A dry body weight (BW) >10.49 Kg in males and >9.95 Kg in females, respectively; - Inpatient or outpatient status at the time of enrolment; - Males or females. Female subjects sexually active must be neither pregnant nor breastfeeding, and must lack childbearing potential from screening visit to the end of the safety follow-up, as defined by using an effective form of contraception (i.e. condoms, oral contraceptives or intra-uterine device-IUD). Medically approved contraception could include abstinence. Oral contraception will be accompanied by a barrier method. A negative serum pregnancy test is required prior to initiation of treatment with study medication. - On stable hemodialysis (HD) or peritoneal dialysis (PD) for their CKD for at least one month before entering the 6-month pre-treatment period; - Plasma iPTH levels > 300 pg/mL, AND - Plasma calcium (Ca) levels > 9.4 mg/dL (with normal serum albumin level), AND - Plasma phosphorus (P) levels <6.5 mg/dL in patients younger than 6 years, or <6.0 mg/dL in older patients, OR - Ca x P product > 60; - Records availability for the following parameters 6 months prior to study entry: demographic information, physical examination, height and dry weight, auxological/anthropometric indices, blood pressure values, Kt/V urea, plasma iPTH, calcium, phosphorus, and alkaline phosphatase levels, blood pH and bicarbonate, serum creatinine/urea, C reactive protein (CRP) levels, liver function tests, blood count, blood 25(OH) vitamin D3 level. |
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E.4 | Principal exclusion criteria |
To be eligible for inclusion in this study the subjects must not meet any of the following criteria at study entry: - The following laboratory values: Hb<9.0 g/dL, WBC<2000/mm3 (2x109/L), platelets <150,000/mm3 (150x109/L) only in subjects who are otherwise eligible for PK/PD assessments; abnormal liver function, defined by a total bilirubin ≥2 times the upper limit of normal values, aspartate aminotransferase, alanine aminotransferase or γ glutamyltranspeptidase (γ-GT) levels ≥2 times the upper limit of normal values. - Any other lab values that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study. - History of malignancy (active malignancy, or off therapy since less than 1 year) - History of diseases causing hypercalcemia (primary hyperparathyroidism; parathyroid carcinoma; Williams syndrome; prolonged immobilization) - Chronic inflammatory diseases (C-Reactive Protein-CRP >2 times the upper limit of normal values) requiring a concomitant corticosteroid or immunosuppressive therapy - History of infectious diseases (including opportunistic infections) within 4 weeks prior to study entry - Evidence as assessed by the Investigator of active or latent bacterial, viral or fungal infections at the time of potential enrollment, including subjects with evidence of Human Immunodeficiency virus (HIV) infection. - Hepatitis-B surface antigen-positive subjects only in subjects who are otherwise eligible for PK/PD assessments - Hepatits C antibody-positive subjects who are also PCR-positive or RIBA positive only in subjects who are otherwise eligible for PK/PD assessments - Use of recombinant human growth hormone therapy - Use of tricyclic antidepressant use - Use of drugs that interact with cinacalcet disposition, such as ketoconazole, itraconazole, telythromycin, voryconazole, ritonavir, rifampin - Previous use of cinacalcet - History of hypersensitivity to any of the ingredients of the study drug. - Use of any investigational drug, device or biologic within 4 weeks prior to study entry or during the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary study endpoint (EP) will be the proportion of recruited patients who will have a reduction from baseline of at least 25% in mean iPTH levels with concomitant values for plasma P <6 mg/dL and Ca between 8.4 and 10.5 mg/dL or the Ca x P product <60 during the 6-month, intra subject-controlled, efficacy-assessment phase. |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
E.8.1.2 | Open | No |
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 |
controllo intra-paziente retrospettivo-prospettico |
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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.8.2.3.1 | Comparator description |
controllo intra-paziente con terapia standard |
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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 | 12 |
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 | Information not present in EudraCT |
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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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 |