SB-681323-Methotrexate Interaction Study

Arthritis, Rheumatoid Clinical Trial

Official title:

A Placebo Controlled Study to Evaluate the Safety and Tolerability of Repeat Doses of SB-681323 in Patients Receiving Methotrexate for Rheumatoid Arthritis.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00419809
• Other study ID #: RA1101607
• Status: Completed
• Phase: Phase 1
• First received: January 5, 2007
• Last updated: May 31, 2012
• Start date: May 2005
• Est. completion date: December 2005

Study information

• Verified date: January 2012
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2005
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 tests.

• 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.

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• SB-681323 oral tablets

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Adelaide
Australia	GSK Investigational Site	Randwick, Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Secondary	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.