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 |
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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 | 17.0 |
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 |
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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 efficacy of cinacalcet for reducing the plasma intact parathyroid hormone (iPTH) level by ≥ 30% |
Valutare l’efficacia di cinacalcet nel ridurre i livelli plasmatici di ormone paratiroideo intatto (iPTH) di ≥30% |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of cinacalcet for lowering the plasma iPTH level to ≤ 300 pg/mL (31.8 pmol/L)
• To evaluate the impact of cinacalcet on corrected total serum calcium level
• To evaluate the impact of cinacalcet on serum phosphorus level |
• Valutare l’efficacia di cinacalcet nel ridurre i livelli plasmatici di iPTH fino a ≤300 pg/mL (31,8 pmol/L)
• • Valutare l’impatto di cinacalcet sui livelli sierici di calcio corretto totale
• • Valutare l’impatto di cinacalcet sui livelli sierici di fosforo |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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.
- Age 6 to < 18 years old at time of randomization
- Diagnosis of CKD, receiving either hemodialysis or peritoneal dialysis for ≥ 30 days prior to screening
- Dry weight ≥ 12.5 kg during screening
- Diagnosis of SHPT with the mean of the 2 consecutive central laboratory iPTH values ≥ 300 pg/mL during screening
- Corrected calcium value ≥ 8.8 mg/dL obtained from the central laboratory during screening
- Dialysate calcium level ≥ 2.5 mEq/L during screening |
• Consenso informato scritto fornito dal genitore o dal rappresentante legalmente riconosciuto e consenso scritto da parte del soggetto in base alle linee guida istituzionali
• Età compresa tra 6 e <18 anni al momento della randomizzazione
• Diagnosi di SHPT con la media dei due valori consecutivi di iPTH emersi dalle analisi del laboratorio centrale ≥300 pg/mL durante lo screening
• Valore di calcio corretto ≥8,8 mg/dL durante lo screening
• Diagnosi di CKD con emodialisi o dialisi peritoneale, per ≥30 giorni prima dello screening
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E.4 | Principal exclusion criteria |
- 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)
- 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
- Subject has known sensitivity to any of the products to be administered during dosing
- 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
- 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
- Subject previously has entered this study
- 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
- Subject is pregnant or breast feeding, or planning to become pregnant during the study or within 9 days after the end of treatment
- History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrythmias or other conditions associated with prolonged QT interval
- Receipt of cinacalcet (within 30 days of screening)
During screening:
- Corrected QT Interval (QTc) > 500 ms, using Bazett’s formula
- 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
- Use of grapefruit juice, herbal medications or potent CYP3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole)
-Use of concomitant medications that may prolong the corrected QT interval (eg, ondansetron, albuterol)
- Receipt of cinacalcet
At time of randomization, scheduled for or expect:
- Renal transplant within 90 days |
• Soggetti sessualmente attivi non disposti a usare un metodo contraccettivo altamente efficace durante il trattamento e per almeno 9 giorni dopo la fine del trattamento
• Soggetti in stato di gravidanza o allattamento, o che sta pianificando una gravidanza durante lo studio o entro 9 giorni dopo la fine del trattamento
• Anamnesi di sindrome congenita del QT lungo, blocco cardiaco, tachiaritmia ventricolare o altre condizioni associate al prolungamento dell’intervallo QT
• Intervallo QT corretto (QTc) >500 ms, secondo la formula di Bazett
• QTc tra ≥450 e ≤500 ms, secondo la formula di Bazett, salvo permesso scritto di arruolamento rilasciato dallo sperimentatore in seguito a un consulto con un cardiologo pediatrico
• Utilizzo di succo di pompelmo, medicinali a base di erbe o potenti inibitori del CYP3A4 (ad es.eritromicina, claritromicina, ketoconazolo, itraconazolo)
• Uso concomitante di medicinali che possono prolungare l’intervallo QTc (ad es. ondansetron, albuterolo)
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E.5 End points |
E.5.1 | Primary end point(s) |
Achievement of a ≥ 30% reduction from baseline in mean plasma iPTH during the efficacy assessment period (EAP), defined as Week 17 – 20. |
Raggiungimento di una riduzione ≥30% rispetto al basale del livello plasmatico medio di iPTH durante il periodo di valutazione dell’efficacia (EAP), che consiste nelle Settimane 17–20. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 17 – 20 |
20 settimane |
|
E.5.2 | Secondary end point(s) |
• Achievement of a mean iPTH ≤ 300 pg/mL (31.8 pmol/L) during the EAP
• Percent change in iPTH from baseline to the mean value during the EAP
• Change in corrected total serum calcium from baseline to the mean value during the EAP
• Change in serum phosphorus from baseline to the mean value during the EAP |
• Raggiungimento di un iPTH medio ≤300 pg/mL (31,8 pmol/L) durante l’EAP
• Variazione percentuale di iPTH tra il basale e il valore medio durante l’EAP
• Variazione dei livelli sierici di calcio corretto totale tra il basale e il valore medio durante l’EAP
• Variazione del fosforo sierico tra il basale e il valore medio durante l’EAP
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|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 17 – 20 |
20 settimane |
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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) | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Standard di cura |
Standard of care |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 30 |
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 |
Austria |
Belgium |
Czech Republic |
France |
Germany |
Greece |
Hungary |
Italy |
Lithuania |
Luxembourg |
Mexico |
Netherlands |
Poland |
Portugal |
Russian Federation |
Slovakia |
South Africa |
Spain |
Switzerland |
Turkey |
Ukraine |
United Kingdom |
United States |
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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
|
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. |
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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 | |
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 months | 6 |