A Study to Investigate the Safety Tolerability Pharmacokinetics, and Pharmacodynamics of Inhaled and Intravenous GSK2862277 in Healthy Volunteers
12 de mayo de 2017 actualizado por: GlaxoSmithKline
A Three Part, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of Inhaled and Intravenous GSK2862277 in Healthy Volunteers
This will be a 3 part study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat doses of GSK2862277 administered via inhalation (IH) or intravenous (IV) routes in healthy subjects.
Part 1 of this study will involve an initial assessment of safety, tolerability and pharmacokinetics of GSK286227, via single escalating intravenous doses, compared to a predecessor molecule, GSK1995057. After completion of Part 1 an interim data review will occur which will assess key comparability criteria to inform progression to Part 2 of the study.
Part 2 of the study will involve single doses of GSK2862277 at a level predicted to be at or close to therapeutic dose levels. Part 2 will investigate both intravenous and inhaled routes of administration, in sequential manner, respectively. An interim data review will also occur after completion of Part 2, where all data accumulated previously will be assessed to examine appropriateness to progress to Part 3.
Part 3 of the study will involve 5 days of repeat dosing via both inhaled and intravenous routes using the same dose administered in Part 2.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
- Droga: Single IV dose of GSK2862277
- Droga: Matching placebo single dose IV infusion
- Droga: Single IH dose of GSK2862277
- Droga: Matching placebo single dose IH
- Droga: Repeat IV dose of GSK2862277
- Droga: Matching placebo repeat dose IV infusion
- Droga: Repeat IH dose selected of GSK2862277 from Part 2
- Droga: Matching placebo repeat dose IH
Tipo de estudio
Intervencionista
Inscripción (Actual)
54
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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Middlesex
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Harrow, Middlesex, Reino Unido, HA13UJ
- GSK Investigational 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 a 65 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Subject is positive at screening for HAVH autoantibodies against GSK1995057 (Part 1 only).
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus (HIV) antibody.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Exclusion Criteria:
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus (HIV) antibody.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day
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: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Part 1: Cohort 1a
Single IV dose of GSK2862277 as a continuous infusion over 2 hours.
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GSK2862277 solution available in a 40 mg vial for IV administration.
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Experimental: Part 1: Cohort 1b
Single IV dose of GSK2862277 as a continuous infusion over 3 hours.
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GSK2862277 solution available in a 40 mg vial for IV administration.
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Experimental: Part 1: Cohort 1c
Single IV dose of GSK2862277 as a continuous infusion over 3 hours.
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GSK2862277 solution available in a 40 mg vial for IV administration.
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Experimental: Part 2: Cohort 2a GSK2862277
Single IV dose of GSK2862277 as a continuous infusion over 1 hour.
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GSK2862277 solution available in a 40 mg vial for IV administration.
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Experimental: Part 2: Cohort 2a Placebo
Matching placebo will be administered as a continuous IV infusion over 1 hour.
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Matching placebo solution available for IV administration.
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Experimental: Part 2: Cohort 2b GSK2862277
Single IH dose of GSK2862277.
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GSK2862277 nebulised solution available in a 40 mg vial for IH administration.
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Experimental: Part 2: Cohort 2b Placebo
Matching placebo will be administered.
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Matching placebo nebulised solution available for IH administration.
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Experimental: Part 3: Cohort 3a GSK2862277
IV dose of GSK2862277 (decided from Part 2) as a continuous infusion over 1 hour for daily 5 days.
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GSK2862277 solution available in a 40 mg vial for IV administration.
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Experimental: Part 3: Cohort 3a Placebo
Matching placebo will be administered as IV infusion over 1 hour daily for 5 days.
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Matching placebo solution available for IV administration.
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Experimental: Part 3: Cohort 3b GSK2862277
Repeat IH dose of GSK2862277 (decided from Part 2) daily for 5 days.
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GSK2862277 nebulised solution available in a 40 mg vial for IH administration.
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Experimental: Part 3: Cohort 3b Placebo
Matching placebo will be administered as IH daily for 5 days.
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Matching placebo nebulised solution available for IH administration.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Safety and tolerability of single IV or IH dose of GSK2862277 assessed by number of subjects with adverse events (AE)s in Part 1 and Part 2
Periodo de tiempo: Up to 42 days
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Safety and tolerability parameters will include recording of adverse events (AEs), throughout the study.
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Up to 42 days
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Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by number of subjects with AEs in Part 3
Periodo de tiempo: Up to 42 days
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Safety and tolerability parameters will include recording of AEs, throughout the study.
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Up to 42 days
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Safety and tolerability of single IV or IH dose of GSK2862277 assessed by laboratory tests in Part 1 and Part 2
Periodo de tiempo: Up to 42 days
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Laboratory tests will include haemogram, clinical chemistry, urine examination.
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Up to 42 days
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Safety and tolerability of repeat IV or IH dose of GSK2862277 as assessed by laboratory tests in Part 3
Periodo de tiempo: Up to 42 days
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Laboratory tests will include haemogram, clinical chemistry, urine examination.
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Up to 42 days
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Safety and tolerability of single IV or IH dose of GSK2862277 assessed by vital signs in Part 1 and Part 2
Periodo de tiempo: Up to 42 days
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Vital signs will include blood pressure (BP), heart rate respiration rate and body temperature.
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Up to 42 days
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Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by vital signs in Part 3
Periodo de tiempo: Up to 42 days
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Vital signs will include BP, heart rate respiration rate and body temperature.
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Up to 42 days
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Safety and tolerability of single IV or IH dose of GSK2862277 assessed by ECG in Part 1 and Part 2
Periodo de tiempo: Up to 42 days
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Safety data will include electrocardiogram (ECG) readings obtained at each timepoint during the study.
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Up to 42 days
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Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by ECG in Part 3
Periodo de tiempo: Up to 42 days
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Safety data will include ECG readings obtained at each timepoint during the study.
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Up to 42 days
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Safety and tolerability of single IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 1 and Part 2
Periodo de tiempo: Up to 42 days
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Spirometry monitoring will include forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).
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Up to 42 days
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Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 3
Periodo de tiempo: Up to 42 days
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Spirometry monitoring will include FEV1 and FVC.
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Up to 42 days
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Safety and tolerability of single IV dose of GSK2862277 as assessed by measurement of plasma cytokines in Part 1
Periodo de tiempo: Up to 42 days
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Blood samples will be collected for assessment of plasma cytokines.
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Up to 42 days
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Immunogenicity in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
Periodo de tiempo: Up to 60 days
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Presence of anti GSK2862277 binding antibodies will be evaluated.
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Up to 60 days
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Immunogenicity in subjects receiving repeat IV or IH dose of GSK2862277 in Part 3
Periodo de tiempo: Up to 60 days
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Presence of anti GSK2862277 binding antibodies will be evaluated.
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Up to 60 days
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Pharmacokinetic (PK) parameters in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
Periodo de tiempo: Up to 48 hours post dose
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The blood samples will be collected for plasma concentrations of GSK2862277.
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Up to 48 hours post dose
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PK parameters in subjects receiving repeat IV dose of GSK2862277 in Part 3 Cohort 3a
Periodo de tiempo: Up to 48 hours post last dose
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The blood samples will be collected for plasma concentrations of GSK2862277.
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Up to 48 hours post last dose
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PK parameters in subjects receiving repeat IH dose of GSK2862277 in Part 3 Cohort 3b
Periodo de tiempo: Up to 48 hours post last dose
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The blood samples will be collected for plasma concentrations of GSK2862277
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Up to 48 hours post last dose
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PK parameters in subjects receiving single IV dose of GSK2862277 in Part 1
Periodo de tiempo: Up to 48 hours post last dose
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The PK parameters will be compared with historic GSK1995057 PK data in Part 1
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Up to 48 hours post last dose
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Pharmacodynamic and immune function biomarkers in serum of subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
Periodo de tiempo: Up to 48 hours post last dose
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The pharmacodynamic and immune function biomarkers in serum.
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Up to 48 hours post last dose
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Pharmacodynamic and immune function biomarkers in serum of subjects receiving repeat IV or IH dose of GSK2862277in Part 3
Periodo de tiempo: Up to 48 hours post last dose
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The pharmacodynamic and immune function biomarkers in serum.
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Up to 48 hours post last dose
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Change from baseline in IL-8 expression in ex vivo WBA in subjects receiving single IV 0.05 mg/kg dose of GSK2862277 in Part 1 in Cohort1c
Periodo de tiempo: Up to 12 hours post dose
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IL-8 expression in ex vivo whole blood essay (WBA).
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Up to 12 hours post dose
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Composite of urine parameters in subjects receiving single IV 2 mg/kg dose of GSK2862277 in Part 2 in Cohort 2a
Periodo de tiempo: Up to 48 hours post dose
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The urine samples will be collected for urine concentrations of GSK2862277.
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Up to 48 hours post dose
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
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.
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)
22 de febrero de 2013
Finalización primaria (Actual)
25 de octubre de 2013
Finalización del estudio (Actual)
25 de octubre de 2013
Fechas de registro del estudio
Enviado por primera vez
14 de febrero de 2013
Primero enviado que cumplió con los criterios de control de calidad
21 de marzo de 2013
Publicado por primera vez (Estimar)
26 de marzo de 2013
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
15 de mayo de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
12 de mayo de 2017
Última verificación
1 de mayo de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 116343
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan IPD
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Datos del estudio/Documentos
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Especificación del conjunto de datos
Identificador de información: 116343Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Conjunto de datos de participantes individuales
Identificador de información: 116343Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Informe de estudio clínico
Identificador de información: 116343Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Formulario de informe de caso anotado
Identificador de información: 116343Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Formulario de consentimiento informado
Identificador de información: 116343Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Plan de Análisis Estadístico
Identificador de información: 116343Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Protocolo de estudio
Identificador de información: 116343Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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. .