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Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Participants With Hepatitis C (MK-2248-002)

5 de junio de 2015 actualizado por: Merck Sharp & Dohme LLC

A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Subjects With Hepatitis C Infection

The objective of this study is to identify a safe dose of MK-2248 in participants with Hepatitis C Virus (HCV) that mediates at least a 3 log10 reduction in viral load (VL) from baseline. It is anticipated that once-daily administration of a safe and well tolerated dose of MK-2248 will reduce VL by at least 3 log10 IU/mL.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

In this Phase 1b study, the pharmacokinetic (PK), pharmacodynamic (PD), and safety profile of MK-2248 in HCV-infected participants will be evaluated as follows: Part I will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (A, B, C, and D). Part II will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (E, F, G, and H). Part III will assess sequentially ascending MK-2248 doses ranging up to ≤800 mg in 2 panels (I and J). The potential relationship between plasma MK-2248 levels and VL reduction will be determined.

Tipo de estudio

Intervencionista

Inscripción (Actual)

13

Fase

  • Fase 1

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 65 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • clinical diagnosis of chronic HCV defined by positive serology for HCV or positive HCV RNA for at least 6 months and detectable HCV RNA in peripheral blood ≥10^5 IU/mL at screening
  • Body Mass Index (BMI) ≥18 to <37 kg/m^2
  • in good health other than HCV infection with normal laboratory values

Exclusion Criteria:

  • history of clinically significant and not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic (excepting HCV infection), immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
  • history of cancer other than adequately treated non-melanomatous skin carcinoma, malignancies which have been successfully treated ≥10 years prior with no recurrence, or cancer that is unlikely to sustain a recurrence for the duration of the trial
  • history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
  • positive for hepatitis B surface antigen or human immunodeficiency virus
  • had major surgery or lost 1 unit of blood within 4 weeks prior to screening
  • QTc interval ≥470 msec (males) or ≥480 msec (females)
  • received prior treatment with other HCV inhibitors
  • clinical or laboratory evidence of decompensated liver 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: Aleatorizado
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Part I: MK-2248 200 mg (Panel A)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
Experimental: Part I: MK-2248 ≤800 mg (Panel B)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
Experimental: Part I: MK-2248 ≤800 mg (Panel C)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth for 7 days.
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
Experimental: Part I: MK-2248 ≤800 mg (Panel D)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
Experimental: Part II: MK-2248 200 mg (Panel E)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
Experimental: Part II: MK-2248 ≤800 mg (Panel F)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
Experimental: Part II: MK-2248 ≤800 mg (Panel G)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
Experimental: Part II: MK-2248 ≤800 mg (Panel H)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
Experimental: Part III: MK-2248 ≤800 mg (Panel I)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
Experimental: Part III: MK-2248 ≤800 mg (Panel J)
Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Maximum change from baseline in VL
Periodo de tiempo: Up to Day 42
Up to Day 42
Number of participants experiencing an adverse event (AE)
Periodo de tiempo: Up to Day 42
Up to Day 42
Number of participants who discontinue from study treatment due to an AE
Periodo de tiempo: Up to Day 7
Up to Day 7

Medidas de resultado secundarias

Medida de resultado
Periodo de tiempo
Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s)
Periodo de tiempo: Up to Day 10
Up to Day 10
Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s)
Periodo de tiempo: Up to Day 10
Up to Day 10
Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)
Periodo de tiempo: Up to Day 10
Up to Day 10
Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs
Periodo de tiempo: Up to Day 10
Up to Day 10
Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma
Periodo de tiempo: Up to Day 10
Up to Day 10
Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma
Periodo de tiempo: Up to Day 10
Up to Day 10
Total clearance (amount of drug cleared relative to the total systemically available amount per unit time [CL/F]) of MK-2248 in plasma
Periodo de tiempo: Up to Day 10
Up to Day 10
Apparent volume of distribution (V/F) of MK-2248 in plasma
Periodo de tiempo: Up to Day 10
Up to Day 10

Colaboradores e Investigadores

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

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 2014

Finalización primaria (Actual)

1 de noviembre de 2014

Finalización del estudio (Actual)

1 de abril de 2015

Fechas de registro del estudio

Enviado por primera vez

10 de junio de 2014

Primero enviado que cumplió con los criterios de control de calidad

10 de junio de 2014

Publicado por primera vez (Estimar)

11 de junio de 2014

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

8 de junio de 2015

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

5 de junio de 2015

Última verificación

1 de junio de 2015

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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