Clinical trial NCT00419809: SB-681323-Methotrexate Interaction Study
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Arthritis, Rheumatoid
Keywords: methotrexate,
SB-681323,
p38 MAP Kinase Inhibitor,
liver function
Rheumatoid Arthritis,
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-01-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: 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 outcomes:
measure: 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.
Other outcomes:
Locations:
city: Randwick, Sydney
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Adelaide
country: Australia
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: