SB-681323-Methotrexate Interaction Study

NCT00419809 | Completed Phase 1

• 1 other identifier: RA1101607
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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

Conditions

Arthritis, Rheumatoid

Keywords

methotrexate,; SB-681323,; p38 MAP Kinase Inhibitor,; liver function; Rheumatoid Arthritis,

Outcome Measures

Primary Outcomes (1)

• 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 (1)

• 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.

Interventions

SB-681323 oral tablets DRUG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Randwick, Sydney, New South Wales, 2031, Australia

Location

GSK Investigational Site

Adelaide, South Australia 5000, Australia

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

dilmapimod

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2007
• First Posted: January 9, 2007
• Study Start: May 1, 2005
• Primary Completion: December 1, 2005
• Study Completion: December 1, 2005
• Last Updated: June 4, 2012

Record last verified: 2012-01

Locations

AU (2)