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To Examine The Effects Of Lapatinib On Orally And Intravenously Administered Midazolam In Cancer Patients

4 de diciembre de 2017 actualizado por: GlaxoSmithKline

A Four-Way Cross-Over Study to Examine the Effects of Lapatinib on the Pharmacokinetics of Orally and Intravenously Administered Midazolam in Cancer Patients

To characterize the effect of repeat oral dose of lapatinib treatment on the pharmacokinetics of a single oral and single intravenous dose of midazolam in adult cancer patients. Also to assess the safety and tolerability of chronic oral lapatinib therapy in cancer patients.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

24

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

    • New Hampshire
      • Lebanon, New Hampshire, Estados Unidos, 03756
        • GSK Investigational Site
    • North Carolina
      • Chapel Hill, North Carolina, Estados Unidos, 27599
        • GSK Investigational Site

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 a 70 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion criteria:

  • Histologically confirmed, solid tumor refractory to standard therapy.
  • Tumor for which there is no standard therapy.
  • Able to swallow and retain oral medication.
  • ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
  • Provided written informed consent.
  • Adequate bone marrow function.
  • Serum creatinine is less than or equal to 1.5 mg/dL.
  • Calculated creatinine clearance is greater than or equal to 60 ml/min based on Cockcroft and Gault.
  • Total bilirubin is greater than or equal to the upper limit of normal of institutional values.
  • Aspartate and alanine transaminase is less than or equal to 3 times the upper limit of the institutional values.
  • Have a left ventricular ejection fraction (LVEF) greater than or equal to 40% based on electrocardiogram (ECHO) or multiple gated acquisition scan (MUGA).
  • Resting oxygen saturations of greater than 90%.

Exclusion criteria:

  • Pregnant or lactating female.
  • Have malabsorption syndrome, a disease affecting gastrointestinal function.
  • Resection of the stomach or small bowel.
  • Evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease.
  • Is considered medically unfit for the study by the investigator as a result of the medical interview, physical exam, or screening investigations.
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational product.
  • Use of anilinoquinazolines, such as gefitinib [Iressa™], erlotinib [Tarceva™].
  • Immediate or delayed hypersensitivity reaction to midazolam or any component of the formulation, including benzyl alcohol (cross-sensitivity with other benzodiazepines may exist).
  • Has narrow-angle glaucoma which is a contraindication to midazolam use.
  • Has received treatment with any investigational drug in the previous 4 weeks.
  • Received chemotherapy, immunotherapy, biologic therapy or hormonal therapy within the past 14 days, with the exception of mitomycin C within the past 6 weeks.
  • Currently receiving amiodarone or has received amiodarone in the 6 months prior to screening.
  • Is taking regular doses of opiates that in the opinion of the investigator would put the patient at risk of clinically significant respiratory compromise when midazolam is administered.
  • Physiological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  • Has Class II to IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  • Clinically significant electrocardiogram (ECG) abnormality.
  • Clinically assessed to have inadequate venous access for protocol-related blood draws.

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 cruzada
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Subjects with cancer

In Part 1 of the study, subjects will be randomized to one of four sequences. All subjects will receive oral or intravenous (IV) midazolam on Days 1, 3, 9 and 11 as per assigned randomization scheme. Starting on Day 4 through Day 11, subjects will receive a daily dose of 1500 milligrams (mg) of oral lapatinib.

In Part 2, which will begin on Day 12, the subjects will be required to take 1500 mg of lapatinib daily until removed from the study for disease progression, adverse events, withdrawal of consent, or transfer to another lapatinib study.

Subjects will receive midazolam by oral or IV route on Days 1, 3, 9 and 11. Oral midazolam was supplied as 3 mg tablets; IV midazolam was supplied as 1 milligram per milliliter (mg/L) sterile solution.
Otros nombres:
  • GW572016 oral tablets
Subjects will receive 1500 mg lapatinib by oral route once daily from Day 4.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Area under the concentration versus time curve (AUC) of midazolam
Periodo de tiempo: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration. AUC of midazolam in the presence and absence of lapatinib will be determined.
Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Maximum observed concentration (Cmax) of midazolam
Periodo de tiempo: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration. Cmax of midazolam in the presence and absence of lapatinib will be determined.
Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Clearance (CL) of midazolam
Periodo de tiempo: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration. CL of midazolam in the presence and absence of lapatinib will be determined.
Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Half-life (t½) of midazolam
Periodo de tiempo: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration. t1/2 of midazolam in the presence and absence of lapatinib will be determined.
Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Absolute bioavailability (F) of midazolam
Periodo de tiempo: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration. Absolute bioavailability of midazolam in the presence and absence of lapatinib will be determined.
Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Time of maximum observed concentration (tmax) of midazolam
Periodo de tiempo: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration.
Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Volume of distribution (Vss) of midazolam
Periodo de tiempo: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration.
Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Periodo de tiempo: Up to Month 7
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events may require medical or surgical intervention to prevent one of the other outcomes listed above.
Up to Month 7
Number of subjects with abnormal clinical chemistry parameters
Periodo de tiempo: Up to Month 7
The following clinical chemistry parameters were evaluated: sodium, potassium, total carbon dioxide (CO2), calcium, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and blood urea nitrogen (BUN).
Up to Month 7
Number of subjects with abnormal hematology parameters
Periodo de tiempo: Up to Month 7
The following hematology parameters were evaluated: hemoglobin, hematocrit, red blood cell count, white blood cell count, neutrophil count, lymphocyte count, monocyte count, eosinophil count and basophil count.
Up to Month 7
Number of subjects with abnormal blood pressure
Periodo de tiempo: Up to Month 7
Systolic and diastolic blood pressure will be measured.
Up to Month 7
Number of subjects with abnormal heart rate
Periodo de tiempo: Up to Month 7
Heart rate will be measured.
Up to Month 7

Colaboradores e Investigadores

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

Patrocinador

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 (Actual)

21 de noviembre de 2005

Finalización primaria (Actual)

8 de febrero de 2007

Finalización del estudio (Actual)

8 de febrero de 2007

Fechas de registro del estudio

Enviado por primera vez

22 de noviembre de 2005

Primero enviado que cumplió con los criterios de control de calidad

23 de noviembre de 2005

Publicado por primera vez (Estimar)

24 de noviembre de 2005

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

6 de diciembre de 2017

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

4 de diciembre de 2017

Última verificación

1 de diciembre de 2017

Más información

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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