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A Single Dose Of Compound SB-681323 Compared To Prednisolone On A Protein That Is an Indicator For Rheumatoid Arthritis

27 de julio de 2017 actualizado por: GlaxoSmithKline

A Randomised, Placebo-controlled, Parallel Group Single Dose Study of SB681323 in Patients With Active RA to Investigate the CRP Dose Response Relationship

This study is designed to compare a range of doses of SB-681323 with prednisolone, which has known effects on rheumatoid arthritis patients. By comparing the two drugs and their effects on blood proteins that indicate for rheumatoid arthritis, we hope to ascertain information on the most effective dose of SB-681323 to use in future.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

77

Fase

  • Fase 2

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

  • Alemania
      • Berlin, Alemania, 14059
        • GSK Investigational Site
      • Berlin, Alemania, 13125
        • GSK Investigational Site
      • Berlin, Alemania, 14109
        • GSK Investigational Site
      • Berlin, Alemania, 12163
        • GSK Investigational Site
    • Baden-Wuerttemberg
      • Villingen-Schwenningen, Baden-Wuerttemberg, Alemania, 78054
        • GSK Investigational Site
    • Niedersachsen
      • Hildesheim, Niedersachsen, Alemania, 31134
        • GSK Investigational Site
    • Sachsen
      • Chemnitz, Sachsen, Alemania, 09111
        • GSK Investigational Site
      • Leipzig, Sachsen, Alemania, 04107
        • GSK Investigational Site
      • Leipzig, Sachsen, Alemania, 04229
        • GSK Investigational Site
  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • GSK Investigational Site
    • Queensland
      • Douglas, Queensland, Australia, 4814
        • GSK Investigational Site
      • Woolloongabba, Queensland, Australia, 4102
        • GSK Investigational Site
    • South Australia
      • Daw Park, South Australia, Australia, 5041
        • GSK Investigational Site
      • Woodville, South Australia, Australia, 5011
        • GSK Investigational Site
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • GSK Investigational Site
    • Western Australia
      • Shenton Park, Western Australia, Australia, 6008
        • GSK Investigational Site
  • Federación Rusa
      • Ekaterinburg, Federación Rusa, 620102
        • GSK Investigational Site
      • Moscow, Federación Rusa, 115522
        • GSK Investigational Site
      • Ryazan, Federación Rusa, 390026
        • GSK Investigational Site
      • Yaroslavl, Federación Rusa, 150003
        • GSK Investigational Site
  • Francia
      • Montpellier Cedex 5, Francia, 34295
        • GSK Investigational Site
    • Picardie
      • Amiens, Picardie, Francia, 80054
        • GSK Investigational Site
  • Reino Unido
      • Oxford, Reino Unido, OX3 7LP
        • GSK Investigational Site
      • Sheffield, Reino Unido, S10 2RX
        • GSK Investigational Site
    • Cambridgeshire
      • Cambridge, Cambridgeshire, Reino Unido, CB2 0QQ
        • GSK Investigational Site
    • Lancashire
      • Wigan, Lancashire, Reino Unido, WN6 9EP
        • GSK Investigational Site
    • Merseyside
      • Liverpool, Merseyside, Reino Unido, L9 7AL
        • GSK Investigational Site
    • Northumberland
      • Newcastle, Northumberland, Reino Unido, NE1 4LP
        • 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 y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion criteria:

  • Must have a diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology.
  • Must have 3 or more swollen or 3 or more tender/painful joints at screening.
  • Must be on stable weekly methotrexate (2.5mg - 25mg) for at least eight weeks prior to screening.

Exclusion criteria:

  • Must not be morbidly obese.

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 paralela
  • Enmascaramiento: Doble

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Analysis for C-Reactive protein (CRP) levels 72 hours post-dose following SB-681323
Periodo de tiempo: Day 3 (at 72 hour)
CRP levels were compared between SB-681323 and placebo 72 hours post-dose. The ratio of the dose response relationship of placebo and 7.5mg, 15mg and 25mg of SB-681323 has been presented.
Day 3 (at 72 hour)

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Analysis of CRP levels 24 and 48 hours post-dose following SB-681323
Periodo de tiempo: Day 1 (at 24 hour) and Day 2 (at 48 hour)
CRP levels were compared between SB-681323 and placebo 24 and 48 hours post-dose. The ratio of the dose response relationship of placebo and 7.5mg, 15mg and 25mg of SB-681323 has been presented.
Day 1 (at 24 hour) and Day 2 (at 48 hour)
Analysis of Interleukin (IL)-6 levels up to 72 hours post-dose following SB-681323
Periodo de tiempo: Upto Day 3 (at 1, 3, 24 and 72 hour)
A blood sample of approximately 5 milliliter (mL) was taken for measurement of serum markers. IL-6 measurements were performed at 1 hour, 3, hours, 24 hours and 72 hours post-dose. The ratio of the dose response relationship of placebo and 7.5mg, 15mg and 25mg of SB-681323 has been presented.
Upto Day 3 (at 1, 3, 24 and 72 hour)
Number of participants with adverse events (AE) and serious adverse events (SAE)
Periodo de tiempo: Upto Day 3 (72 hours)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as 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, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury. There were no SAEs reported in this study.
Upto Day 3 (72 hours)
Change from Baseline in vital sign systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Periodo de tiempo: Baseline (at pre-dose Day 0) and Day 3 (at 90 minutes, 3 hour, 24 and 72 hour)
Supine vital signs SBP and DBP were recorded whilst the participant was in a supine position (participant lying flat with maximum one pillow) having rested in that position for at least 10 minutes before each reading. Measurements were performed at 90 minutes, 3 hours, 24 hours and 72 hours post-dose. Baseline was defined as assessment performed pre-dose at Day 0. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values at the time of assessment.
Baseline (at pre-dose Day 0) and Day 3 (at 90 minutes, 3 hour, 24 and 72 hour)
Change from Baseline in vital sign heart rate
Periodo de tiempo: Baseline (at pre-dose Day 0) and Day 3 (at 90 minutes, 3 hour, 24 and 72 hour)
Supine vital signs (heart rate) was recorded whilst the participant was in a supine position (participant lying flat with maximum one pillow) having rested in that position for at least 10 minutes before each reading. Measurements were performed at 90 minutes, 3 hours, 24 hours and 72 hours post-dose. Baseline was defined as assessment performed pre-dose at Day 0. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values at the time of assessment.
Baseline (at pre-dose Day 0) and Day 3 (at 90 minutes, 3 hour, 24 and 72 hour)
Number of participants with abnormal electrocardiogram (ECG) findings
Periodo de tiempo: Day 1 (pre-dose, 1 hour and 3 hour)
Full 12-lead ECGs were recorded using an ECG machine that automatically calculated the pulse rate and measured PR, RR, QRS, QT, QTc(b) intervals (Bazett's correction was applied to QTc measurements). Measurements were carried out at pre-dose, 1 hour and 3 hours on Day 1. ECG findings were characterized as abnormal-not clinically significant (A-NCS) and abnormal-clinically significant (A-CS). Data has been presented for A-NCS findings on Day 1.
Day 1 (pre-dose, 1 hour and 3 hour)
Number of participants with clinical chemistry data outside the clinical concern range
Periodo de tiempo: Upto Day 3 (pre-dose, 24, 48 and 72 hours
Clinical chemistry parameters included albumin, alkaline phosphatase, alanine amino transferase, indirect bilirubin, calcium, chloride, creatinine, gamma glutamyl transferase, glucose, potassium, lactate dehydrogenase, triglycerides. Measurements were carried out at pre-dose, 24 hours, 48 hours and 72 hours. Data for number of participants with values outside clinical concern range defined as high and low have been presented.
Upto Day 3 (pre-dose, 24, 48 and 72 hours
Number of participants with hematology data outside the clinical concern
Periodo de tiempo: Upto Day 3 (pre-dose, 24 and 72 hours)
Hematology parameters included eosinophils, hemoglobin, hematocrit, lymphocytes, mean corpuscle hemoglobin, mean corpuscle volume, platelet count, reticulocytes, white blood cell count (WBC). Measurements were carried out at pre-dose, 24 hours and 72 hours. Data for number of participants with values outside clinical concern range defined as high and low have been presented.
Upto Day 3 (pre-dose, 24 and 72 hours)
Number of participants with abnormal urinalysis dipstick results
Periodo de tiempo: Upto Day 3 (pre-dose, 24 and 72 hours)
Approximately 10-20 mL mid-stream urine was collected into a sterile container and was screened by dipstick for: occult blood, proteins, ketones, glucose, red blood cells (RBC) and WBC. Sediment microscopy was performed only if any of the Multi-stick tests were abnormal. In such cases, microscopy was performed for: WBC, RBC, hyaline casts, granular casts, cellular casts. Data for number of participants with abnormal urinalysis results for positive parameters as assessed by dipstick and microscopic analysis have been presented.
Upto Day 3 (pre-dose, 24 and 72 hours)
Whole blood messenger RNA (mRNA) levels of tumor necrosis factor alpha [TNF-α], IL-8, IL-1β and Cyclo-oxygenase-2 [COX-2] (and other genes implicated in the pathogenesis of RA or genes involved in the mode of action of the compounds administered)
Periodo de tiempo: Pre-dose, 45 minutes, 90 minutes and 3 hours on Day 1
Blood samples were taken for extraction of whole blood mRNA (2 x 2.5mL PAXgene tubes). The samples were taken at the time-points pre-dose, 45 minutes, 90 minutes and 3 hours. Messenger RNA levels for various markers was measured. These markers included Prednisolone markers: DDIT4, DUSP1, FKBP5, GILZ, IL1R2, TXNIP, ZNF145 and p38 markers: COX2, IFI30, IL1b, IL6, IL8, TNF. An aliquot of mRNA was stored for later analysis of other genes associated with the pathogenesis of RA and in the mode of action of the compounds administered.
Pre-dose, 45 minutes, 90 minutes and 3 hours on Day 1

Colaboradores e Investigadores

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

Patrocinador

GlaxoSmithKline

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 junio de 2005

Finalización primaria (Actual)

3 de agosto de 2006

Finalización del estudio (Actual)

3 de agosto de 2006

Fechas de registro del estudio

Enviado por primera vez

24 de agosto de 2005

Primero enviado que cumplió con los criterios de control de calidad

24 de agosto de 2005

Publicado por primera vez (Estimar)

25 de agosto de 2005

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

31 de julio de 2017

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

27 de julio de 2017

Última verificación

1 de julio de 2017

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • RA1104046

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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