E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary Hyperparathyroidism and Chronic Kidney Disease Receiving
Dialysis |
Gestione dell’iperparatiroidismo secondario (SHPT) nei soggetti pediatrici con malattia renale cronica (CKD) in dialisi |
|
E.1.1.1 | Medical condition in easily understood language |
Secondary Hyperparathyroidism and Chronic Kidney Disease |
Gestione dell’iperparatiroidismo secondario (SHPT) nei soggetti pediatrici con malattia renale cronica (CKD) in dialisi |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020708 |
E.1.2 | Term | Hyperparathyroidism secondary |
E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
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 characterize the long-term safety and tolerability of cinacalcet in pediatric subjects with CKD receiving dialysis |
Determinare la sicurezza e la tollerabilità a lungo termine di cinacalcet in soggetti pediatrici con CKD dializzati |
|
E.2.2 | Secondary objectives of the trial |
To characterize the long-term effect of cinacalcet in pediatric subjects receiving dialysis on laboratory parameters associated with CKD-MBD |
Determinare l'effetto a lungo termine di cinacalcet sui parametri di laboratorio associati a osteodistrofia renale (CKD-MBD) in soggetti pediatrici dializzati
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
101 Subject’s legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated.
102 Subject must complete treatment through Week 20 in parent study 20130356
103 Dry weight > 12.5 kg at Day 1
104 The mean iPTH value (Week19 in 20130356) ≥ 300 pg/mL (Standard of Care arm)
105 Corrected calcium value (Week 19 in 2010356) ≥ 8.8 mg/dL (Standard of Care arm)
106 Dialysate calcium ≥ 2.5 mEq/L at Day 1
|
I soggetti che completeranno il periodo di trattamento di
20 settimane nello studio originario 20130356 saranno eleggibili a ricevere 28 settimane di trattamento
con cinacalcet in questo studio di estensione. Per essere eleggibili i soggetti dovranno inoltre soddisfare
i criteri di inclusione ed esclusione di questo studio di estensione. I soggetti dovranno fornire un
consenso informato scritto (genitori o tutore) e un assenso, se pertinente, in base alle normative locali
specifiche per le procedure di questo studio. I soggetti arruolati nel braccio dello studio 20130356 in
trattamento con lo standard di cura saranno eleggibili a partecipare allo studio di estensione se alla
visita della settimana 19 i livelli di iPTH saranno ≥ 300 pg/ml e i livelli di cCa saranno ≥ 8,8 mg/ml. I
soggetti eleggibili provenienti dal braccio dello studio 20130356 trattato con cinacalcet proseguiranno il
trattamento con cinacalcet in base alle regole di somministrazione illustrate nel paragrafo 6.2.3..
|
|
E.4 | Principal exclusion criteria |
201 Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).
202 Other investigational procedures while participating in this study are excluded.
203 Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years.
204 Subject has known sensitivity to any of the products to be administered during dosing
205 Subject likely to not be available to complete all protocol required study visits or procedures, and/or to comply with all required study procedures (eg, electronic patient diary) to the best of the subject and investigator’s knowledge
206 History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
207 Subject previously has entered this study.
208 If sexually active, subject is not willing to use highly effective contraception during treatment and for at least 9 days after the end of treatment
209 Subject is pregnant or breast feeding, or planning to become pregnant during the study or within 9 days after the end of treatment
210 History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrythmias or other conditions associated with prolonged QT interval
At Day 1 Study Visit
211 Subject has a clinically significant (in the opinion of the investigator) or severe (grade ≥ 3 CTCAE v 4.0) ongoing adverse event related to IP from Study 20130356
212 Corrected QT Interval (QTc) > 500 ms, using Bazett’s formula
213 QTc ≥ 450 to ≤ 500 ms, using Bazett’s formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist
214 Use of grapefruit juice, herbal medications or CYP3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole)
215 Use of concomitant medications that may prolong the corrected QT interval (eg, ondansetron, albuterol)
|
Saranno esclusi da questo studio i soggetti che mostreranno eventi avversi che si protraggono dallo studio
20130356, che sono ritenuti correlati al prodotto sperimentale e hanno un grado CTCAE ≥ 3 e/o sono
ritenuti clinicamente significativi dallo sperimentatore. Per un elenco completo dei criteri di eleggibilità, consultare il paragrafo 4.1 e il paragrafo 4.1.2
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary analysis will be based on Safety Analysis Set. of missing data will be utilized Subject incidence of the primary endpoint will be reported. Events of interest (including hypocalcemia, convulsions/seizure, hypotension, cardiac failure, hypersensitivity, ischemic heart disease, fracture, acute pancreatitis, drug-related hepatic disorders, nervous system disorders (excluding seizures), neoplastic events, QT prolongation/ ventricular tachyarrhythmia, and infection) will be categorized and summarized by parent study treatment group. |
Incidenza di eventi avversi di interesse che emergono con il trattamento |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
DURING THE STUDY |
durante tutto lo studio |
|
E.5.2 | Secondary end point(s) |
The primary analysis will be based on FAS for all secondary endpoints. Summary statistics will be provided for percent change in PTH, iPTH, from baseline to week 3, week 7, week 11, week 15, week 19, week 23, and week 28 within the study population and each age group by previous treatment group in the parent study and overall. No missing data imputation will be used. Summary statistics will be provided for serum cCa and phosphorus values from baseline to week 3, week 7, week 11, week 15, week 19, week 23, and week 28 within the study population and each age group by previous treatment group in the parent study and overall. No imputation of missing data will be utilized.
Additional summary statistics to include iPTH, cCa, and P values from the baseline of the parent study over time to end of this study will also be provided for subjects who are treated with cinacalcet in both studies
|
•Variazione percentuale dal giorno 1 alla settimana 11 e alla settimana 28 dei livelli dell'ormone
paratiroideo intatto (iPTH)
•Valori corretti del calcio (cCa) il giorno 1 della settimana 11 e della settimana 28
•Valori sierici del fosforo il giorno 1 della settimana 11 e della settimana 28
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
DAY 1 OF WEEK 11 AND OF WEEK 28 |
al giorno 1 della settimana 11 e della settimana 28 |
|
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 | No |
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) | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 26 |
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 | No |
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 |
Belgium |
Czech Republic |
France |
Germany |
Greece |
Hungary |
Italy |
Lithuania |
Mexico |
New Zealand |
Poland |
Portugal |
Russian Federation |
Slovakia |
Spain |
Ukraine |
United States |
|
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
|
End of Study per protocol is defined as when the last subject is assessed or receives an intervention for the purposes of final collection of data. |
La fine dello studio si verifica quando l'ultimo soggetto è valutato o riceve un intervento ai fini della raccolta di dati definitivi riguardanti lo studio. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |