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Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Parathyroid Hormone Levels in Children Aged 10-16 With Chronic Kidney Disease (CKD)

1 de junio de 2018 actualizado por: AbbVie (prior sponsor, Abbott)

A Phase 3, Prospective, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Intact Parathyroid Hormone Levels in Pediatric Subjects Ages 10 to 16 Years With Moderate to Severe Chronic Kidney Disease

Part 1: To determine the safety, tolerability, and pharmacokinetics of a single dose of 3 μg paricalcitol capsules in children ages 10 to 16 years with moderate to severe chronic kidney disease (CKD Stages 3 and 4).

Part 2: To determine the safety and efficacy of paricalcitol capsules as compared to placebo in decreasing serum intact parathyroid hormone (iPTH) in children ages 10 to 16 years with moderate to severe chronic kidney disease with an initial 12 weeks of double-blinded study drug followed by a minimum of 12 weeks of open-label active drug.

Descripción general del estudio

Estado

Terminado

Intervención / Tratamiento

Descripción detallada

The study consists of two parts. Part 1 is an open-label single-dose, non-fasting, multicenter study to evaluate the pharmacokinetics (PK) of paricalcitol capsules in 12 children ages 10 to 16 years with CKD Stages 3 and 4. Part 2 of this study will be conducted as a 12 week randomized double-blind, placebo-controlled study, followed by 12 weeks open-label treatment. Participants active or enrolled under amendment 5 will enter a follow-up period and have study visits every 4 weeks until the final participant reaches Week 24.

Tipo de estudio

Intervencionista

Inscripción (Actual)

47

Fase

  • Fase 3

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

10 años a 16 años (Niño)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Subject has chronic kidney disease Stage 3 or 4 as determined by estimated glomerular filtration rate (15 to 59 mL/min/1.73 m²) at Screening.
  • Subject is not expected to begin dialysis for at least 6 months (in the opinion of the investigator).
  • For entry into the Washout Period (for subjects who are currently on a vitamin D receptor activator [VDRA] and need to complete a 2 to 4 week washout), the subject must satisfy the following criteria based on the Screening laboratory values:

    • estimated glomerular filtration rate between 15 to 59 mL/min/1.73 m².
    • iPTH measurement that is greater than or equal to 60 pg/mL (Stage 3 subjects) or greater than or equal to 90 pg/mL (Stage 4 subjects).
    • An adjusted serum calcium value greater than or equal to 8.2 mg/dL (2.05 mmol/L) to less than or equal to 10.5 mg/dL (2.63 mmol/L).
    • A serum phosphorus value greater than or equal to 2.0 mg/dL (0.65 mmol/L but less than or equal to 6.0 mg/dL (1.94 mmol/L).
  • For entry into the Treatment Phase (vitamin D receptor activator naïve subjects and those that have completed a 4 week washout), the subject must have:

    • iPTH measurement that is greater than or equal to 75 pg/mL (Stage 3 subjects) or greater than or equal to 110 pg/mL (Stage 4 subjects).
    • An adjusted serum calcium value greater than or equal to 8.4 mg/dL (2.10 mmol/L) but less than or equal to 10.2 mg/dL (2.55 mmol/L).
    • A serum phosphorus value greater than or equal to 2.5 mg/dL (0.81 mmol/L) but less than or equal to 5.8 mg/dL (1.87 mmol/L).
    • Must have 25-hydroxyvitamin D levels ≥ 30 ng/mL prior to washout, if not VDRA naïve, or treatment in Part II of the study.

Exclusion Criteria:

  • All subjects that have had a small bowel transplant will be excluded from the study.
  • Subject has had acute kidney failure within 12 weeks of the Screening Phase (defined as an acute rise in serum creatinine).
  • Subject has had symptomatic or significant hypocalcemia requiring active vitamin D therapy (for example, calcitriol, paricalcitol, doxercalciferol or alfacalcidol) within 6 months prior to the Screening Phase.
  • Subject has a history of active kidney stones (6 months prior to screening).
  • Subject has chronic gastrointestinal disease, which in the investigator's opinion may cause significant gastrointestinal malabsorption.
  • Subject is taking maintenance calcitonin, bisphosphonates, cinacalcet, glucocorticoids in an equivalent dose of greater than 5 mg prednisone daily, or other drugs known to affect calcium or bone metabolism within 4 weeks prior to treatment.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Doble

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Part 1: Paricalcitol
Participants received a single 3 µg dose of paricalcitol capsules on Study Day 1.
Paricalcitol capsules taken with water.
Otros nombres:
  • Zemplar
Comparador de placebos: Part 2: Placebo
Participants received placebo capsules three times a week (TIW) for 12 weeks during the double-blind treatment phase. From Weeks 12 to 24 participants received open-label paricalcitol at an initial dose of 1 µg three times a week. Doses could be increased in 1 μg increments every 4 weeks based on chemistry evaluations to target Kidney Disease Outcomes Quality Initiatives (KDOQI) target levels.
Paricalcitol capsules taken with water.
Otros nombres:
  • Zemplar
Placebo capsules taken with water
Experimental: Part 2: Paricalcitol
Participants received paricalcitol three times a week for 12 weeks during the double-blind treatment period and during the open-label period (Weeks 12-24). The initial dose of paricalcitol was 1 µg TIW. Doses could be increased in 1 μg increments every 4 weeks based on chemistry evaluations to target KDOQI target levels.
Paricalcitol capsules taken with water.
Otros nombres:
  • Zemplar

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Part 1: Paricalcitol Maximum Observed Plasma Concentration (Cmax)
Periodo de tiempo: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
Part 1: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞)
Periodo de tiempo: Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
Blood samples were collected at hour 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 hours after dosing.
Part 2: Percentage of Participants Achieving Two Consecutive Reductions at Least 30% From Baseline in iPTH
Periodo de tiempo: 12-week double-blind treatment period
The primary efficacy endpoint was the percentage of participants who achieved two consecutive ≥ 30% reductions from baseline in intact parathyroid hormone (iPTH) levels during the 12 week double-blind portion of the study regardless of CKD stage.
12-week double-blind treatment period

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Part 2: Percentage of Participants Achieving a Final iPTH Within KDOQI Target Ranges
Periodo de tiempo: Week 12

The Kidney Disease Outcomes Quality Initiatives (KDOQI) Pediatric Subcommittee on Practice Guidelines for Bone Metabolism and Disease in Children with CKD target range for intact parathyroid hormone (iPTH) is as follows::

CKD Stage 3: 35 - 69 pg/mL; CKD Stage 4: 70 - 110 pg/mL.

Week 12
Part 2: Change From Baseline in iPTH to Each Post-baseline Visit
Periodo de tiempo: Baseline and Weeks 2, 4, 8 and 12
Baseline and Weeks 2, 4, 8 and 12
Part 2: Percentage of Participants Achieving Final Calcium Levels Within KDOQI Target Ranges
Periodo de tiempo: Week 12

KDOQI recommends serum calcium is maintained within age appropriate normal ranges:

Age 6 - 12: 9.4 - 10.2 mg/dL (2.35 - 2.55 mmol/L); Age 13 - 20: 8.8 - 10.2 mg/dL (2.20 - 2.55 mmol/L).

Week 12
Part 2: Percentage of Participants Achieving Final Phosphorus Levels Within KDOQI Target Ranges
Periodo de tiempo: Week 12

The KDOQI target ranges of serum phosphorus are to maintain at or above age appropriate lower limits and no higher than the age-appropriate upper limits:

Age 6 - 12: 3.6 - 5.8 mg/dL (1.16 - 1.87 mmol/L); Age 13 - 20: 2.3 - 4.5 mg/dL (0.74 - 1.45 mmol/L).

Week 12
Part 2: Change From Baseline in First Morning Void (FMV) Urinary Albumin to Creatinine Ratio (UACR)
Periodo de tiempo: Baseline and Weeks 4, 8 and 12
The mean change from Baseline in FMV UACR on a log scale to each post baseline visit.
Baseline and Weeks 4, 8 and 12

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Investigadores

  • Director de estudio: Deepa Chand, MD, AbbVie

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Enlaces Útiles

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de febrero de 2010

Finalización primaria (Actual)

1 de mayo de 2014

Finalización del estudio (Actual)

1 de diciembre de 2014

Fechas de registro del estudio

Enviado por primera vez

13 de noviembre de 2009

Primero enviado que cumplió con los criterios de control de calidad

20 de noviembre de 2009

Publicado por primera vez (Estimar)

24 de noviembre de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

2 de julio de 2018

Última actualización enviada que cumplió con los criterios de control de calidad

1 de junio de 2018

Última verificación

1 de febrero de 2017

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • M10-149
  • 2010-019439-37 (Número EudraCT)

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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