| 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 e insuficiencia renal crónica (IRC) en diálisis. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Secondary Hyperparathyroidism and Chronic Kidney Disease |
| Hiperparatiroidismo secundario e insuficiencia renal crónica |
|
| 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 | 18.0 |
| 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 |
|
| 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 |
| Describir la seguridad y tolerabilidad a largo plazo de cinacalcet en sujetos pediátricos con insuficiencia renal crónica (IRC) sometidos a diálisis. |
|
| 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 |
| Describir el efecto a largo plazo de cinacalcet en los parámetros analíticos relacionados con las alteraciones minerales y óseas asociadas a la insuficiencia renal crónica (CKD-MBD) en sujetos pediátricos sometidos a diálisis. |
|
| 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 concentration ≥ 2.5 mEq/L at day 1 |
101 El representante legal autorizado del sujeto ha dado su consentimiento informado cuando el sujeto es demasiado joven legalmente 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 el día 1.
102 Tratamiento completado hasta la semana 20 del estudio original 20130356.
103 Peso seco ≥ 12,5 kg el día 1
104 Concentración de calcio en el dializado ≥ 2,5 mEq/L el día 1
Solo los sujetos aleatorizados en el grupo de tratamiento estándar del estudio 20130356
105 Valor de la PTHi ≥ 300 pg/mL (semana 19 del estudio 20130356)
106 Valor del calcio corregido ≥ 8,8 mg/dL (semana 19 del estudio 20130356) |
|
| 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) or CYP2D6 substrates (eg,flecainide, propafenone, metoprolol, desipramine, nortriptyline, clomipramine)
215 Use of concomitant medications that may prolong the corrected QT interval (eg, ondansetron, albuterol)
At Day 1 Study Visit-Subjects Randomized to the 20130356 Cinacalcet Arm Only
217 Cinacalcet dose withheld > 1 month |
201 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, aparte del estudio 20130356 de Amgen.
202 Están excluidos otros procedimientos experimentales durante la participación en este estudio.
203 Tumor maligno, excepto cáncer de piel no melanomatoso o carcinoma cervical o ductal de mama in situ, en los últimos 5 años.
204 El sujeto presenta una sensibilidad conocida a alguno de los productos que se administrarán durante la dosificación.
205 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 [diario-e]).
206 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.
207 El sujeto ya ha sido incluido anteriormente en este estudio.
208 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.
209 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.
210 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.
Visita del día 1 del estudio-Todos los sujetos
211 El sujeto presenta un acontecimiento adverso en curso del estudio 20130356 que se considera relacionado con el PI y:
? Es de grado ≥ 3 según los CTCAE (v 4.0) y/o
? En opinión del investigador se considera clínicamente significativo.
212 Los valores del laboratorio central (Cac, PTHi) no se obtuvieron/no están disponibles en la semana 19 del estudio 20130356.
213 Intervalo QT corregido (QTc) > 500 ms, utilizando la fórmula de Bazett.
214 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.
215 Uso de zumo de pomelo, fitomedicamentos, inhibidores de CYP3A4 (p. ej., eritromicina, claritromicina, ketoconazol e itraconazol) o sustratos de CYP2D6 (p. ej., flecainida, propafenona, metoprolol, desipramina, nortriptilina, clomipramina).
216 Uso de medicaciones concomitantes que pueden prolongar el intervalo QTc (p. ej., ondansetrón y albuterol).
Visita del día 1 del estudio-Solo los sujetos aleatorizados al grupo de cinacalcet en el estudio 20130356
217 La dosis cinacalcet se suspendió > 1 mes.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is subject incidence of events of interest (EOI; hypocalcemia, convulsions, hypotension, worsening of heart failure, hypersensitivity, ischemic heart disease, QT prolongation/ventricular tachyarrhytmias, fracture, acute pancreatitis, drug-related hepatic disorders, nervous system disorders [excluding seizures], neoplastic events, and infection). |
| La variable principal es la incidencia en el sujeto de acontecimientos de interés (EOI); p. ej., hipocalcemia, convulsiones, hipotensión, empeoramiento de la insuficiencia cardíaca, hipersensibilidad, cardiopatía isquémica, prolongación del QT/taquiarritmias ventriculares, fracturas, pancreatitis aguda, trastornos hepáticos relacionados con el fármaco, trastornos del sistema nervioso [excepto las convulsiones], acontecimientos neoplásicos e infección). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At the end of the study |
| Al finalizar el estudio |
|
| 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 |
| El análisis principal se basará en el GAC para todas las variables secundarias. Se proporcionarán estadísticas de resumen para el cambio porcentual en la PTHi desde el día 1 hasta la semana 11 y la semana 28 dentro de la población del estudio y en cada grupo de edad según el grupo de tratamiento previo en el estudio original y en conjunto. No se utilizará la imputación de datos ausentes. Se proporcionarán estadísticas de resumen para los valores de Cac y fósforo séricos del día 1 hasta la semana 11 y la semana 28 dentro de la población del estudio y dentro de cada grupo de edad por grupo de tratamiento previo en el estudio original y en conjunto. No se utilizará la imputación de datos ausentes. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| At various timepoints throughout the study. |
| En varios momentos a lo largo del estudio. |
|
| 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 | 2 |
| 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. |
| El fin del estudio se define como el momento en que el último sujeto se evalúa o recibe una intervención con la intención de recopilar los últimos datos. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 8 |
| 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 |
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