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A Pharmacokinetics (PK) Study to Investigate the Effect of Rifampin on PK of Vemurafenib (Zelboraf)

21 de octubre de 2016 actualizado por: Hoffmann-La Roche

A Phase I, Open-Label, Multicenter, Three-Period, One-Sequence Study to Investigate the Effect of Rifampin on the Pharmacokinetics of a Single Oral Dose of 960 mg of Vemurafenib

This open-label, multi-center, three-period, one-sequence study will investigate the effect of rifampin on the PK of vemurafenib in participants with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options. Eligible participants will have the option to continue treatment with vemurafenib as part of an extension study GO28399 (NCT01739764).

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

27

Fase

  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Brasil
    • RS
      • Porto Alegre, RS, Brasil, 90035-003
      • Porto Alegre, RS, Brasil, 90020-090
      • Porto Alegre, RS, Brasil, 90840-440
  • Croacia
      • Varazdin, Croacia, 42000
      • Zagreb, Croacia, 10000
  • Egipto
      • Alexandria, Egipto, 21131
      • Cairo, Egipto, 11796
      • Dakahlia, Egipto, 324
      • Tanta, Egipto
  • Estados Unidos
    • Arkansas
      • Rogers, Arkansas, Estados Unidos, 72758
    • California
      • Pleasant Hill, California, Estados Unidos, 94523
    • Ohio
      • Middletown, Ohio, Estados Unidos, 45042
    • Texas
      • Dallas, Texas, Estados Unidos, 75246
  • Sudáfrica
      • Cape Town, Sudáfrica, 7570
      • Port Elizabeth, Sudáfrica, 6045

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

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Participants with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAF V600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a Deoxyribonucleic acid (DNA) sequencing method, and who have no acceptable standard treatment options
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Life expectancy of greater than or equal to (>/=) 12 weeks
  • Full recovery from the effects of any major surgery or significant traumatic injury within 14 days prior to the first dose of study treatment
  • Adequate hematologic and end organ function
  • Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use 2 effective methods of contraception
  • Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential

Exclusion Criteria:

  • Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug
  • Requirement for immediate or urgent treatment with daily vemurafenib and for whom the intermittent schedule of vemurafenib employed during the 24-day period for this trial is not clinically acceptable
  • Allergy or hypersensitivity to components of the vemurafenib formulation
  • Experimental therapy within 4 weeks prior to first dose of study drug
  • Major surgical procedure or significant traumatic injury within 14 days prior to first dose of study drug, or anticipation of the need for major surgery during study treatment
  • Prior anti-cancer therapy within 28 days before the first dose of study drug
  • History of clinically significant cardiac or pulmonary dysfunction
  • History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment
  • History of myocardial infarction within 6 months prior to first dose of study drug
  • Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
  • History of congenital long QT syndrome or corrected QT interval (QTc) greater than (>) 450 milliseconds
  • Active central nervous system lesions
  • Uncontrolled or poorly controlled diabetes
  • Current severe, uncontrolled systemic disease

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: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Vemurafenib + Rifampin
There will be 3 intervention periods in the study: Period A (Days 1 to 7), Period B (Days 8 to 16), and Period C (Days 17 to 24). Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 milligrams (mg) as film-coated tablets orally alone on Day 1 (Period A); with rifampin (at a dose of 600 mg as capsules orally) on Day 17 (Period C); and rifampin alone at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).
Droga: Rifampin
Rifampin at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 23 (Periods B and C).
Droga: Vemurafenib
Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 mg as film-coated tablets orally on Day 1 (Period A) and on Day 17 (Period C).
Otros nombres:
  • RO5185426, Zelboraf

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Area Under the Plasma Concentration Time-curve From Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib
Periodo de tiempo: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
AUClast is the area under the vemurafenib plasma concentration versus time curve from time zero to the time of last measured concentration of vemurafenib (Tlast). Area under the curve (AUC) is a measure of the plasma concentration of a drug over time. AUClast is presented in micrograms times (*) hour per milliliter (mcg*h/mL).
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Area Under the Plasma Concentration Time-curve From Zero to Extrapolated Infinite Time (AUC[0-inf]) of Vemurafenib
Periodo de tiempo: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
AUC(0-inf) is the AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in mcg*h/mL.
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Maximum Observed Plasma Concentration (Cmax) of Vemurafenib
Periodo de tiempo: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Cmax is the maximum observed plasma vemurafenib concentration, presented in microgram per milliliter (mcg/mL).
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
Time to Reach Cmax (Tmax) of Vemurafenib
Periodo de tiempo: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Tmax is the time from vemurafenib administration to reach Cmax for vemurafenib.
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Plasma Elimination Half Life (t1/2) of Vemurafenib
Periodo de tiempo: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Plasma elimination half-life is the time measured during drug elimination phase for the plasma drug concentration to decrease by one half.
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Plasma Apparent Clearance (CL/F) of Vemurafenib
Periodo de tiempo: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Clearance of a drug is a measure of the rate at which a drug is removed (metabolized or eliminated by normal biological processes) from the blood. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Area Under the Plasma Concentration Time-curve From Zero to 168 Hours [AUC(0-168)] of Vemurafenib
Periodo de tiempo: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
AUC(0-168) is the AUC from time zero (pre-dose) to 168 hours (time point for last blood sample collection). AUC is a measure of the plasma concentration of a drug over time. AUC(0-168) is presented in mcg*h/mL.
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Percent Extrapolated AUC(0-inf) (AUCpeo) of Vemurafenib
Periodo de tiempo: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
The AUCpeo, that is, percent area obtained after extrapolation from Tlast to infinity is calculated by using the formula AUCpeo = 100*(AUC[0-inf] minus AUC[0-last])/AUC(0-inf). This parameter provides information about what percentage of the theoretical curve AUC(0-inf) is possible to determine experimentally (AUC0-last).
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)

Colaboradores e Investigadores

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

Patrocinador

Hoffmann-La Roche

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 julio de 2013

Finalización primaria (Actual)

1 de noviembre de 2015

Finalización del estudio (Actual)

1 de noviembre de 2015

Fechas de registro del estudio

Enviado por primera vez

9 de enero de 2013

Primero enviado que cumplió con los criterios de control de calidad

9 de enero de 2013

Publicado por primera vez (Estimar)

10 de enero de 2013

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

15 de diciembre de 2016

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

21 de octubre de 2016

Última verificación

1 de octubre de 2016

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • GO28052
  • 2012-003142-33 (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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