To Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib in Renal Impaired Subjects and Healthy Subjects
29 de junio de 2015 actualizado por: AstraZeneca
An Open Label Comparative Study of the Pharmacokinetics, Safety and Tolerability of Selumetinib (AZD6244, ARRY 142886) (Hyd Sulfate) Following a Single Oral Dose in Subjects With Renal Impairment and Healthy Subjects
A study to assess the pharmacokinetics, safety and tolerability of Selumetinib (AZD6244, ARRY-142886) in subjects with renal impairment and healthy subjects
Descripción general del estudio
Descripción detallada
An open label study to assess the pharmacokinetics, safety and tolerability of 50 mg single oral dose of Selumetinib (AZD6244, ARRY-142886) in subjects with renal impairment and healthy subjects
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
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Florida
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Orlando, Florida, Estados Unidos
- Research Site
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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 all participants:
- Male and female (non childbearing potential) subjects aged 18 years or more with suitable veins for cannulation or repeated venipuncture.
Have a weight of at least 50 kg (110 lbs) and body mass index (BMI) between 18 and 40 kg/m2, inclusive.
Inclusion healthy volunteers only:
Must be in good health as determined by a medical history, physical examination, 12 lead ECG, clinical laboratory evaluations, and an ophthalmic examination performed before the administration of the investigational product.
Inclusion renal impaired patients only:
- Stable renal function
Exclusion Criteria all participants:
- Subjects of Japanese or non Japanese Asian ethnicity.
- Any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese Asian (e.g. China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia). Asian Indians are acceptable.
- Subjects who smoke more than 10 cigarettes or the equivalent in tobacco per day
In the opinion of the investigator, any evidence of additional severe or uncontrolled systemic disease (eg, currently unstable or uncompensated hepatic, cardiovascular, or respiratory disease) or laboratory finding, physical examination, hematology, clinical chemistry, urinalysis, vital signs, or 12-lead ECG that makes it undesirable for the subject to participate in the study.
Exclusion renal impaired patients only:
- Subjects with an active renal transplant (subjects who have previously received a renal transplant and are currently undergoing dialysis due to transplant failure may be enrolled).
- Acute coronary syndrome within 6 months prior to administration of the investigational product.
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: Ciencia básica
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: HV selumetinib Stage 1
Healthy volunteer (HV)group to receive selumetinib 50mg (2x25mg) orally
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selumetinib 50 mg (2x25mg) administered by mouth as capsules
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Experimental: ESRD selumetinib Stage 1
End stage renal disease (ESRD)patients to recieve selumetinib 50mg (2x25mg) orally
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selumetinib 50 mg (2x25mg) administered by mouth as capsules
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Experimental: Selumetinib stage 2
If deemed necessary patients with mild and/or moderate and/or severe renal impairment will recieve selumetinib 50mg(2x25mg) orally
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selumetinib 50 mg (2x25mg) administered by mouth as capsules
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Description of the pharmacokinetic(PK) profile in terms of maximum observed plasma concentration (Cmax)
Periodo de tiempo: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of area under plasma concentration-time curve from zero extrapolated to infinity (AUC)
Periodo de tiempo: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of area under plasma concentration-time curve to time of last measurable concentration (AUC[0-t]) for selumetinib if AUC is not reportable in more than 80% of subjects
Periodo de tiempo: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Description of the safety profile in terms of adverse events, physical examinations, ophthalmologic assessments, vital signs, clinical laboratory assessments and 12-lead electrocardiograms.
Periodo de tiempo: From screening until follow up. Approximately 6 weeks for healthy volunteers and 8 weeks for renal patients
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From screening until follow up. Approximately 6 weeks for healthy volunteers and 8 weeks for renal patients
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Description of the PK profile in terms of time to reach maximum observed concentration administration (tmax)
Periodo de tiempo: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of area under the plasma concentration time curve from zero to 12 hours postdose (AUC[0-12])
Periodo de tiempo: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h, and12h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h, and12h
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Description of PK profile in terms of terminal rate constant (λz), terminal elimination half-life (t1/2), apparent oral clearance (CL/F)
Periodo de tiempo: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of apparent volume of distribution at steady state (Vss/F) and apparent volume of distribution during the terminal phase (Vz/F)
Periodo de tiempo: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of mean residence time (MRT) and fraction unbound (fu), free Cmax (Cmax, u), free AUC (AUCu), free AUC(0-t) (AUC[0-t],u) and unbound CL/F (CL/Fu)
Periodo de tiempo: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of the amount of drug excreted in urine (Ae) the fraction of dose excreted in urine (fe), renal clearance (CLR) for selumetinib and AUC, Cmax, tmax, t1/2, λz, AUC(0-12) and AUC(0-t)
Periodo de tiempo: The urine collection intervals will be from -12 to 0 (predose), and 0 to 6, 6 to 12, 12 to 24, 24 to 36, 36 to
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These collection will be taken on visit 2 for the healthy volunteers and on visit 2 and 3 if the patients can produce urine
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The urine collection intervals will be from -12 to 0 (predose), and 0 to 6, 6 to 12, 12 to 24, 24 to 36, 36 to
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Description of the PK profile in terms of the metabolite to parent AUC and Cmax ratios (MRAUC and MRCmax)
Periodo de tiempo: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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These samples will be taken on visit 2 for the healthy volunteers and on both visit 2 and visit 3
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of the PK profile in terms of Ae, fe, and CLR for N-desmethyl selumetinib (and the amide metabolite, if deemed appropriate)
Periodo de tiempo: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of the PK profile in terms of time-matched area under the plasma concentration time curve from 1 to 5 hours postdose (AUC[1-5])
Periodo de tiempo: Sample taken predose, at 1h just before dialyse and at 5h after the end of the dialyse
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This will only be taken at the visit when dose is given 1h before dialyse start
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Sample taken predose, at 1h just before dialyse and at 5h after the end of the dialyse
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Description of the PK profile in terms of cumulative amount extracted during dialysis (Ad[1-5]), and dialysis clearance (CLD)
Periodo de tiempo: Samples taken from dialysate collections over 1 hour intervals throughout the entire (approximately 4 hours) dialysis period ie, 0 to 1, 1 to 2, 2 to 3, 3
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This will only be collected during visit 2 and only on end stage renal disease patients
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Samples taken from dialysate collections over 1 hour intervals throughout the entire (approximately 4 hours) dialysis period ie, 0 to 1, 1 to 2, 2 to 3, 3
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Thomas C Marbury, MD, Orlando Clinical Research Centre, US
- Director de estudio: Ian Smith, MD, Astrazeneca United kingdom
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 marzo de 2014
Finalización primaria (Actual)
1 de julio de 2014
Finalización del estudio (Actual)
1 de julio de 2014
Fechas de registro del estudio
Enviado por primera vez
13 de febrero de 2014
Primero enviado que cumplió con los criterios de control de calidad
13 de febrero de 2014
Publicado por primera vez (Estimar)
14 de febrero de 2014
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
30 de junio de 2015
Última actualización enviada que cumplió con los criterios de control de calidad
29 de junio de 2015
Última verificación
1 de junio de 2015
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- D1532C00081
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. .