SB-681323-Methotrexate Interaction Study

Study Description

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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

Condition or disease	Intervention/treatment	Phase
Arthritis, Rheumatoid	Drug: SB-681323 oral tablets	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	18 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
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 Start Date :	May 2005
Actual Primary Completion Date :	December 2005
Actual Study Completion Date :	December 2005

Arms and Interventions

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Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

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 Outcome Measures :

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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

Australia, New South Wales
GSK Investigational Site
Randwick, Sydney, New South Wales, Australia, 2031
Australia
GSK Investigational Site
Adelaide, Australia, South Australia 5000

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00419809 History of Changes
Other Study ID Numbers:	RA1101607
First Posted:	January 9, 2007
Last Update Posted:	June 4, 2012
Last Verified:	January 2012

Keywords provided by GlaxoSmithKline:

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

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Methotrexate; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents	Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors