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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00134693
First Posted: August 25, 2005
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
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.

Condition Intervention Phase
Arthritis, Rheumatoid Drug: Prednisolone Drug: SB-681323 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Placebo-controlled, Parallel Group Single Dose Study of SB681323 in Patients With Active RA to Investigate the CRP Dose Response Relationship

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Analysis for C-Reactive protein (CRP) levels 72 hours post-dose following SB-681323 [ Time Frame: 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.


Secondary Outcome Measures:
  • Analysis of CRP levels 24 and 48 hours post-dose following SB-681323 [ Time Frame: 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.

  • Analysis of Interleukin (IL)-6 levels up to 72 hours post-dose following SB-681323 [ Time Frame: 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.

  • Number of participants with adverse events (AE) and serious adverse events (SAE) [ Time Frame: 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.

  • Change from Baseline in vital sign systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: 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.

  • Change from Baseline in vital sign heart rate [ Time Frame: 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.

  • Number of participants with abnormal electrocardiogram (ECG) findings [ Time Frame: 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.

  • Number of participants with clinical chemistry data outside the clinical concern range [ Time Frame: 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.

  • Number of participants with hematology data outside the clinical concern [ Time Frame: 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.

  • Number of participants with abnormal urinalysis dipstick results [ Time Frame: 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.

  • 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) [ Time Frame: 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.


Enrollment: 77
Actual Study Start Date: June 21, 2005
Study Completion Date: August 3, 2006
Primary Completion Date: August 3, 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Prednisolone Drug: SB-681323
    Other Name: Prednisolone
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00134693


Locations
Australia, New South Wales
GSK Investigational Site
Darlinghurst, New South Wales, Australia, 2010
Australia, Queensland
GSK Investigational Site
Douglas, Queensland, Australia, 4814
GSK Investigational Site
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
GSK Investigational Site
Daw Park, South Australia, Australia, 5041
GSK Investigational Site
Woodville, South Australia, Australia, 5011
Australia, Tasmania
GSK Investigational Site
Hobart, Tasmania, Australia, 7000
Australia, Western Australia
GSK Investigational Site
Shenton Park, Western Australia, Australia, 6008
France
GSK Investigational Site
Amiens, Picardie, France, 80054
GSK Investigational Site
Montpellier Cedex 5, France, 34295
Germany
GSK Investigational Site
Villingen-Schwenningen, Baden-Wuerttemberg, Germany, 78054
GSK Investigational Site
Hildesheim, Niedersachsen, Germany, 31134
GSK Investigational Site
Chemnitz, Sachsen, Germany, 09111
GSK Investigational Site
Leipzig, Sachsen, Germany, 04107
GSK Investigational Site
Leipzig, Sachsen, Germany, 04229
GSK Investigational Site
Berlin, Germany, 12163
GSK Investigational Site
Berlin, Germany, 13125
GSK Investigational Site
Berlin, Germany, 14059
GSK Investigational Site
Berlin, Germany, 14109
Russian Federation
GSK Investigational Site
Ekaterinburg, Russian Federation, 620102
GSK Investigational Site
Moscow, Russian Federation, 115522
GSK Investigational Site
Ryazan, Russian Federation, 390026
GSK Investigational Site
Yaroslavl, Russian Federation, 150003
United Kingdom
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
GSK Investigational Site
Wigan, Lancashire, United Kingdom, WN6 9EP
GSK Investigational Site
Liverpool, Merseyside, United Kingdom, L9 7AL
GSK Investigational Site
Newcastle, Northumberland, United Kingdom, NE1 4LP
GSK Investigational Site
Oxford, United Kingdom, OX3 7LP
GSK Investigational Site
Sheffield, United Kingdom, S10 2RX
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00134693     History of Changes
Other Study ID Numbers: RA1104046
First Submitted: August 24, 2005
First Posted: August 25, 2005
Last Update Posted: October 12, 2017
Last Verified: July 2017

Keywords provided by GlaxoSmithKline:
SB-681323 rheumatoid arthritis CRP biomarkers

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Prednisolone acetate
Methylprednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents