E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary Hyperparathyroidism and Chronic Kidney Disease Receiving Dialysis |
Hiperparatiroidismo secundario (HPTS) Insuficiencia renal crónica (IRC) sometidos a diálisis. |
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E.1.1.1 | Medical condition in easily understood language |
Secondary Hyperparathyroidism and Chronic Kidney Disease |
Hiperparatiroidismo secundario e Insuficiencia renal crónica. |
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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% |
Evaluar la eficacia de cinacalcet para reducir el nivel plasmático de hormona paratiroidea intacta (PTHi) en ≥ 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 |
- Evaluar la eficacia de cinacalcet para reducir el nivel plasmático de PTHi a ≤ 300 pg/mL (31,8 pmol/L).
- Evaluar el impacto de cinacalcet en el nivel de calcio sérico total corregido.
- Evaluar el impacto de cinacalcet en el nivel de fósforo sérico.
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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 ≥ 25.0 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 |
- El representante legal autorizado del sujeto ha dado su consentimiento informado cuando el sujeto es legalmente demasiado joven para dar su consentimiento informado y el sujeto ha dado su asentimiento por escrito de acuerdo con las normativas y/o directrices locales antes de iniciar cualquier actividad/procedimiento específico del estudio.
- Edad de 6 a < 18 años en el momento de la aleatorización.
- Diagnóstico de IRC, con hemodiálisis o diálisis peritoneal, durante ≥ 30 días antes de la selección.
- Peso seco ≥ 25,0 kg durante la selección.
- Diagnóstico de HPTS con la media de 2 valores de PTHi consecutivos del laboratorio central ≥ 300 pg/mL durante la selección.
- Valor de calcio corregido ≥ 8,8 mg/dL obtenido del laboratorio central durante la selección.
Nivel de calcio en el dializado ≥ 2,5 mEq/L durante la selección.
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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 |
-Estar recibiendo actualmente tratamiento en otro estudio de un fármaco o dispositivo en investigación o haber transcurrido menos de 30 días desde el fin del tratamiento en otro estudio de un fármaco o dispositivo en investigación.
-Quedan excluidos otros procedimientos experimentales durante la participación en este estudio.
-Tumor maligno, excepto cáncer de piel no melanomatoso y carcinoma cervical o ductal de mama in situ, en los últimos 5 años.
-El sujeto presenta una sensibilidad conocida a alguno de los productos que se administrarán durante la dosificación.
-Según informan el sujeto y el investigador, es posible que el sujeto no esté disponible para completar todas las visitas o procedimientos del estudio requeridos por el protocolo y/o cumplir todos los procedimientos del estudio (p. ej., diario electrónico del paciente).
-Antecedentes o evidencia de cualquier otro trastorno, condición o enfermedad clínicamente significativo (excepto los indicados anteriormente) que, en opinión del investigador o del médico de Amgen, si se le consulta, pudieran suponer un riesgo para la seguridad del sujeto o interferir en la evaluación, los procedimientos o la realización del estudio.
-El sujeto ya ha sido incluido anteriormente en este estudio.
-Si el sujeto es sexualmente activo y no está dispuesto a utilizar métodos anticonceptivos altamente eficaces durante el tratamiento y durante al menos 9 días después de finalizar el tratamiento.
-Mujer embarazada o en período de lactancia, o que planee quedarse embarazada durante el estudio o en los 9 días posteriores al fin del tratamiento.
-Antecedentes de síndrome de QT largo congénito, bloqueo cardíaco de segundo o tercer grado, taquiarritmias ventriculares u otras enfermedades asociadas a un intervalo QT prolongado.
-En los 30 días anteriores a la selección
Recepción de cinacalcet.
-Durante la selección
Intervalo QT corregido (QTc) > 500 ms, utilizando la fórmula de Bazett.
QTc de ≥ 450 a ≤ 500 ms, utilizando la fórmula de Bazett, a no ser que el investigador dé su permiso por escrito para la inclusión tras consultar con un cardiólogo pediátrico.
Uso de zumo de pomelo, fitomedicamentos o inhibidores potentes de CYP3A4 (p. ej., eritromicina, claritromicina, ketoconazol e itraconazol).
Uso de medicaciones concomitantes que pueden prolongar el intervalo QT corregido (p. ej., ondansetrón y albuterol).
Recepción de cinacalcet.
-En el momento de la aleatorización, programada o prevista
Trasplante renal en los 90 días posteriores. |
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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. |
Consecución de una reducción ≥ 30% desde el nivel basal en la PTHi plasmática media durante el período de evaluación de la eficacia (PEE), definido como el período comprendido entre las semanas 17 y 20. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 17 – 20 |
Semanas 17-20 |
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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 |
-Consecución de una PTHi media ≤ 300 pg/mL (31,8 pmol/L) durante el PEE.
-Cambio porcentual en la PTHi desde el nivel basal hasta el valor medio durante el PEE.
-Cambio en el calcio sérico total corregido desde el nivel basal hasta el valor medio durante el PEE.
-Cambio en el fósforo sérico desde el nivel basal hasta el valor medio durante el PEE.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 17 – 20 |
Semanas 17-20 |
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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 |
Tratamiento Estandar |
Standard of care |
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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 | 2 |
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
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When the last subject is assessed or receives an intervention for the purposes of final collection of data |
El fin del estudio es la fecha de finalización principal. Se define como el momento en que el último sujeto se evalúa o recibe una intervención con la intención de recopilar los últimos datos para el análisis principal. |
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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 |