E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary hyperparathyroidism in subjects with chronic kidney disease |
Iperparatiroidismo secondario nei
soggetti con insufficienza renale cronica
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|
E.1.1.1 | Medical condition in easily understood language |
Hyperparathyroidism (high levels of parathyroid hormone) secondary to chronic kidney disease |
Iperparatiroidismo
(livelli alti di ormone paratiroideo) secondario nei soggetti con insufficienza renale cronica
|
|
E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020706 |
E.1.2 | Term | Hyperparathyroidism NOS |
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 AMG 416 in the treatment of SHPT in subjects with chronic kidney disease on hemodialysis. |
Determinare la sicurezza e la tollerabilità a lungo termine di AMG 416 nel trattamento dell'iperparatiroidismo secondario in soggetti con insufficienza renale cronica sottoposti ad emodialisi. |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives are to characterize the long-term efficacy of AMG 416 on intact parathyroid hormone (iPTH), corrected calcium (cCa), corrected calcium-phosphorus product (cCa x P), and phosphorus |
Determinare l'efficacia a lungo termine di AMG 416 sui livelli di ormone paratiroideo intatto (iPTH), calcio corretto (cCa), prodotto calcio-fosforo corretto (cCa x P) e fosforo. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject understands the study procedures and agrees to participate in the study by giving written informed consent.
• Subject must complete the treatment and follow-up period, or have been discontinued for rising iPTH, from an AMG 416 phase 3 parent study prior to the start of dosing in this study.
• Subject agrees to not participate in another study of an investigational agent during the study.
• Dialysis prescription dialysate calcium concentration must be ≥ 2.25 mEq/L.
• Female subject who is post menopausal (post menopausal is defined as no menses for the previous 1 year and over the age of 50 years), surgically sterilized, has a medical condition that prevents pregnancy, remains abstinent, or is willing to use highly effective contraception during the study and for 3 months after the last dose. Women of child-bearing potential must
have a negative serum pregnancy test within 2 weeks prior to the first dose of AMG 416.
• Male subject is willing to use highly effective contraception when sexually active and will not donate sperm during the treatment phase and for 3 months after the last dose.
• Subject’s legally acceptable representative has provided informed consent when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent. |
• Il soggetto deve capire le procedure dello studio e acconsentire a parteciparvi fornendone consenso informato scritto.
• Prima di iniziare la somministrazione prevista da questo studio il soggetto deve aver completato il trattamento e il periodo di follow-up, o essere stato sospeso dal trattamento per l'aumento dei valori di iPTH, in uno dei 2 studi con AMG 416 di fase 3
• Il soggetto accetta di non partecipare ad un altro studio con un farmaco sperimentale durante il corso dello studio
• La concentrazione prescritta di calcio nel dialisato deve essere ≥ 2,25 mEq/L
• Soggetto di sesso femminile in post menopausa (si definisce post menopausa l'assenza di mestruazioni nell'anno precedente e un'età superiore ai 50 anni), sottoposto a sterilizzazione chirurgica, o che presenti una condizione medica che impedisca la gravidanza, pratichi l'astinenza o si impegni ad adottare un metodo contraccettivo ad elevata efficacia durante lo studio e per i 3 mesi successivi l'ultima dose. Le donne in età fertile devono presentare un test di gravidanza sul siero negativo nei 30 giorni precedenti alla prima dose di AMG 416.
• Soggetto di sesso maschile disposto ad adottare un metodo contraccettivo ad elevata efficacia durante i rapporti sessuali e a non donare sperma durante la fase di trattamento e per i 3 mesi successivi all'ultima dose.
. Il rappresentante legalmente riconosciuto del paziente abbia fornito il consenso informato quando il soggetto abbia qualche condizione che, a giudizio dello sperimentatore, possa compromettere il soggetto di dare consenso scritto
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E.4 | Principal exclusion criteria |
• Currently receiving treatment in another investigational device or drug study.
• Currently receiving other investigational procedures while participating in this study.
• Subject has known sensitivity to any of the products or components to be administered during dosing.
• Subject has received cinacalcet between the last dose of investigational product in the parent study (20120229 or 20120230) and the start of dosing with AMG 416 in the current study.
• Subject has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator.
• Subject has a history of any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject.
• Subject has a serious concurrent medical condition (eg, malignancy) likely to result in death during the next 12 months.
• Subject is pregnant or nursing.
• 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. |
-Soggetti attualmente in trattamento in un altro studio su un dispositivo o un farmaco sperimentale.
- Soggetto attualmente sottoposto ad altre procedure sperimentali durante la partecipazione a questo studio.
- Soggetto che abbia qualsiasi tipo di sensibilità nota per il prodotto in studio o qualsiasi componente che verrà somministrato.
- Soggetto cui sia stato somministrato cinacalcet nell'intervallo tra l'ultima dose di prodotto sperimentale nello studio principale (20120229 o 20120230) e l'inizio della somministrazione nello studio attuale.
- Il soggetto presenta una condizione di instabilità medica sulla base della storia medica, di un esame obiettivo ed esami di laboratorio di routine o è comunque instabile a giudizio dello sperimentatore
- Soggetto con anamnesi di una malattia che, secondo il parere dello sperimentatore, potrebbe confondere i risultati dello studio o rappresentare un rischio aggiuntivo per il soggetto.
- Soggetto con una grave condizione medica concomitante (per es. tumore maligno) che possa esitare in decesso nei 12 mesi successivi.
- Soggetto in stato di gravidanza o in allattamento.
- Il soggetto soffre di un qualsiasi disturbo, condizione o patologia (ad eccezione di quelle sopra riportate) che a giudizio dello sperimentatore possano mettere a rischio il paziente o interferire la valutazione , le procedure o il completamento dello risultati dello studio
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|
E.5 End points |
E.5.1 | Primary end point(s) |
• nature, frequency, severity, and relationship to treatment of all adverse events reported throughout the study
• vital signs and changes in laboratory parameters, including clinical chemistry
• evaluation of antibody formation to AMG 416 |
• natura, frequenza, gravità e rapporto con il trattamento di tutti gli eventi avversi riportati durante tutta la durata dello studio;
• segni vitali e variazioni dei parametri di laboratorio, compresi i parametri chimico clinici;
• ricerca di eventuali anticorpi anti AMG 416.
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|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the efficacy assessment phase |
Durante la fase di valutazione dell'efficacia |
|
E.5.2 | Secondary end point(s) |
• proportion of subjects with > 30% reduction from baseline in predialysis iPTH during the efficacy assessment phase (EAP) and the EAP at 12 months (EAP12)
• proportion of subjects with predialysis iPTH ≤ 300 pg/mL during the EAP and EAP12
• percent change from baseline in predialysis iPTH during the EAP and EAP12
• percent change from baseline in predialysis serum cCa during the EAP and EAP12
• percent change from baseline in predialysis cCa x P during the EAP and EAP12
• percent change from baseline in predialysis serum phosphorus during the EAP and EAP12 |
• percentuale di soggetti con livelli predialisi di iPTH ≤ 300 pg/mL durante la fase EAP ed EAP12
• variazione percentuale rispetto al basale dei livelli predialisi di iPTH durante la fase EAP ed EAP12
• variazione percentuale rispetto al basale dei livelli sierici predialisi di cCa durante la fase EAP ed EAP12
• variazione percentuale rispetto al basale dei livelli predialisi di cCa x P durante la fase EAP ed EAP12
• variazione percentuale rispetto al basale dei livelli sierici predialisi di fosforo durante la fase EAP ed EAP12
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|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the efficacy assessment phase |
Durante la fase di valutazione dell'efficacia |
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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 | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 115 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Netherlands |
Poland |
Russian Federation |
Spain |
Sweden |
United Kingdom |
United States |
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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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LVLS |
Ultima visita dell'ultimo paziente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |