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

Arthritis, Rheumatoid Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00134693
• Other study ID #: RA1104046
• Status: Completed
• Phase: Phase 2
• First received: August 24, 2005
• Last updated: July 27, 2017
• Start date: June 21, 2005
• Est. completion date: August 3, 2006

Study information

• Verified date: July 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: August 3, 2006
• Est. primary completion date: August 3, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Prednisolone

• SB-681323

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Darlinghurst	New South Wales
Australia	GSK Investigational Site	Daw Park	South Australia
Australia	GSK Investigational Site	Douglas	Queensland
Australia	GSK Investigational Site	Hobart	Tasmania
Australia	GSK Investigational Site	Shenton Park	Western Australia
Australia	GSK Investigational Site	Woodville	South Australia
Australia	GSK Investigational Site	Woolloongabba	Queensland
France	GSK Investigational Site	Amiens	Picardie
France	GSK Investigational Site	Montpellier Cedex 5
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Chemnitz	Sachsen
Germany	GSK Investigational Site	Hildesheim	Niedersachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Villingen-Schwenningen	Baden-Wuerttemberg
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	Yaroslavl
United Kingdom	GSK Investigational Site	Cambridge	Cambridgeshire
United Kingdom	GSK Investigational Site	Liverpool	Merseyside
United Kingdom	GSK Investigational Site	Newcastle	Northumberland
United Kingdom	GSK Investigational Site	Oxford
United Kingdom	GSK Investigational Site	Sheffield
United Kingdom	GSK Investigational Site	Wigan	Lancashire

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Australia,  France,  Germany,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analysis for C-Reactive protein (CRP) levels 72 hours post-dose following SB-681323	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)
Secondary	Analysis of CRP levels 24 and 48 hours post-dose following SB-681323	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)
Secondary	Analysis of Interleukin (IL)-6 levels up to 72 hours post-dose following SB-681323	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)
Secondary	Number of participants with adverse events (AE) and serious adverse events (SAE)	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)
Secondary	Change from Baseline in vital sign systolic blood pressure (SBP) and diastolic blood pressure (DBP)	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)
Secondary	Change from Baseline in vital sign heart rate	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)
Secondary	Number of participants with abnormal electrocardiogram (ECG) findings	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)
Secondary	Number of participants with clinical chemistry data outside the clinical concern range	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
Secondary	Number of participants with hematology data outside the clinical concern	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)
Secondary	Number of participants with abnormal urinalysis dipstick results	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)
Secondary	Whole blood messenger RNA (mRNA) levels of tumor necrosis factor alpha [TNF-a], IL-8, IL-1ß 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)	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