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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00134693




Registration number
NCT00134693
Ethics application status
Date submitted
24/08/2005
Date registered
25/08/2005
Date last updated
31/07/2017

Titles & IDs
Public title
A Single Dose Of Compound SB-681323 Compared To Prednisolone On A Protein That Is an Indicator For Rheumatoid Arthritis
Scientific title
A Randomised, Placebo-controlled, Parallel Group Single Dose Study of SB681323 in Patients With Active RA to Investigate the CRP Dose Response Relationship
Secondary ID [1] 0 0
RA1104046
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arthritis, Rheumatoid 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Prednisolone
Treatment: Drugs - SB-681323

Treatment: Drugs: Prednisolone


Treatment: Drugs: SB-681323


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Day 3 (at 72 hour)
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Day 1 (at 24 hour) and Day 2 (at 48 hour)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Upto Day 3 (at 1, 3, 24 and 72 hour)
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Upto Day 3 (72 hours)
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline (at pre-dose Day 0) and Day 3 (at 90 minutes, 3 hour, 24 and 72 hour)
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline (at pre-dose Day 0) and Day 3 (at 90 minutes, 3 hour, 24 and 72 hour)
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Day 1 (pre-dose, 1 hour and 3 hour)
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Upto Day 3 (pre-dose, 24, 48 and 72 hours
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Upto Day 3 (pre-dose, 24 and 72 hours)
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Upto Day 3 (pre-dose, 24 and 72 hours)
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Pre-dose, 45 minutes, 90 minutes and 3 hours on Day 1

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Must not be morbidly obese.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [2] 0 0
GSK Investigational Site - Douglas
Recruitment hospital [3] 0 0
GSK Investigational Site - Woolloongabba
Recruitment hospital [4] 0 0
GSK Investigational Site - Daw Park
Recruitment hospital [5] 0 0
GSK Investigational Site - Woodville
Recruitment hospital [6] 0 0
GSK Investigational Site - Hobart
Recruitment hospital [7] 0 0
GSK Investigational Site - Shenton Park
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
4814 - Douglas
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5041 - Daw Park
Recruitment postcode(s) [5] 0 0
5011 - Woodville
Recruitment postcode(s) [6] 0 0
7000 - Hobart
Recruitment postcode(s) [7] 0 0
6008 - Shenton Park
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Picardie
Country [2] 0 0
France
State/province [2] 0 0
Montpellier Cedex 5
Country [3] 0 0
Germany
State/province [3] 0 0
Baden-Wuerttemberg
Country [4] 0 0
Germany
State/province [4] 0 0
Niedersachsen
Country [5] 0 0
Germany
State/province [5] 0 0
Sachsen
Country [6] 0 0
Germany
State/province [6] 0 0
Berlin
Country [7] 0 0
Russian Federation
State/province [7] 0 0
Ekaterinburg
Country [8] 0 0
Russian Federation
State/province [8] 0 0
Moscow
Country [9] 0 0
Russian Federation
State/province [9] 0 0
Ryazan
Country [10] 0 0
Russian Federation
State/province [10] 0 0
Yaroslavl
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Cambridgeshire
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Lancashire
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Merseyside
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Northumberland
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Oxford
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT00134693
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications