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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from

For full trial details, please see the original record at

Registration number
Ethics application status
Date submitted
Date registered
Date last updated

Titles & IDs
Public title
SB-681323-Methotrexate Interaction Study
Scientific title
A Placebo Controlled Study to Evaluate the Safety and Tolerability of Repeat Doses of SB-681323 in Patients Receiving Methotrexate for Rheumatoid Arthritis.
Secondary ID [1] 0 0
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
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Study type
Description of intervention(s) / exposure
Treatment: Drugs - SB-681323 oral tablets

Treatment: Drugs: SB-681323 oral tablets

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

Primary outcome [1] 0 0
The primary outcome measure is the values of liver function tests following dosing with methotrexate alone (Day 1) and methotrexate and SB-681323 or placebo (Day 15).
Timepoint [1] 0 0
Secondary outcome [1] 0 0
The other comparisons of interest is the pharmacokinetics of methotrexate when dosed alone (Day 1) relative to when dosed with SB681323 (Day 15) pharmacodynamics (effect of SB-681323 on CRP & IL-6 at Days 1, 8 and 15.
Timepoint [1] 0 0

Key inclusion criteria
- Male or female. Females must be of non-child-bearing capacity

- BMI 19 - 30 kg/m2 (inclusive)

- Diagnosis of RA according to the revised 1987 criteria of the American College of
Rheumatology (ACR)

- Negative urine drugs of abuse screen, breath alcohol tests, hepatitis B and C, and HIV

- Liver function tests within normal limits

- Must be on a stable dose of methotrexate (2.5 - 25 mg/week) for >8 weeks prior to
enrolment and which will not be changed during the course of this study.

- Must be on stable folate supplements for >8 weeks prior to enrolment with normal red
cell folate levels at enrollment.
Minimum age
18 Years
Maximum age
75 Years
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
- History of alcohol &/or drug abuse

- Abnormal ECGs at screening

- Liver disease, uncontrolled hypertension, diabetes mellitus, psoriasis, history of
peptic ulcer disease

- The patient is using glucocorticoid at doses >10mg/day.

- The patient is using sulphasalazine at a dose >3g/day.

- The patient is using hydroxychloroquine at a dose >400mg/day.

- The patient is on treatment regimen of DMARDs other than MTX plus one or both of
sulphasalazine and hydrochloroquine (e.g. leflunomide)

- The patient dose of NSAIDs, COX-2 inhibitors or glucocorticoids change at any time
during 2 weeks prior to enrolment until the end of the clinical phase of the study

Study design
Purpose of the study
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
Other design features
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick, Sydney
Recruitment hospital [2] 0 0
GSK Investigational Site - Adelaide
Recruitment postcode(s) [1] 0 0
2031 - Randwick, Sydney
Recruitment postcode(s) [2] 0 0
South Australia 5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry

Ethics approval
Ethics application status

Brief summary
SB-681323 is a p38 MAP-kinase inhibitor that has potential uses in inflammatory conditions
such as RA. Previous p38 MAP-kinase inhibitors have been hindered in development by liver
toxicity. Methotrexate (common treatment for RA patients) also has potential liver toxicity.
This study was an enabling study to determine the safety of co-administration of the two
compounds with respect to liver function
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
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