SB-681323-Methotrexate Interaction Study
This study has been completed.
Information provided by (Responsible Party):
First received: January 5, 2007
Last updated: May 31, 2012
Last verified: January 2012
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
Drug: SB-681323 oral tablets
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
||A Placebo Controlled Study to Evaluate the Safety and Tolerability of Repeat Doses of SB-681323 in Patients Receiving Methotrexate for Rheumatoid Arthritis.
Primary Outcome Measures:
- 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:
- 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.
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||December 2005 (Final data collection date for primary outcome measure)
|Ages Eligible for Study:
||18 Years to 75 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- 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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00419809
|GSK Investigational Site
|Randwick, Sydney, New South Wales, Australia, 2031 |
|GSK Investigational Site
|Adelaide, Australia, South Australia 5000 |
||GSK Clinical Trials
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||January 5, 2007
||May 31, 2012
||Australia: Department of Health and Ageing Therapeutic Goods Administration
Keywords provided by GlaxoSmithKline:
p38 MAP Kinase Inhibitor,
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on September 16, 2014
Connective Tissue Diseases
Immune System Diseases
Abortifacient Agents, Nonsteroidal
Reproductive Control Agents
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors