Study Of 90mg Of GW274150 In Subjects Over 50 Years, Who Have Rheumatoid Arthritis (RA)

GlaxoSmithKline (GSK)

Status and phase

Completed

Phase 2

Conditions

Arthritis, Rheumatoid

Treatments

Drug: GW274150

Study type

Interventional

Funder types

Industry

Identifiers

NCT00370435

104916

Details and patient eligibility

About

This is a study of GW274150, an iNOS (inducible nitric oxide synthase) inhibitor to investigate safety, tolerability and pharmacokinetics (PK) in the rheumatoid arthritis (RA) population (greater than 50 years). Safety, tolerability and PK of GW274150 in an adult and elderly population have not yet been determined. Therefore this study is designed to ensure that 90mg GW274150 will be safe and well-tolerated in this adult and elderly RA patient population on methotrexate. The assessments will include pharmacokinetics (PK), liver function tests and creatinine clearance.

This study will provide confidence that a single 90mg dose of GW274150 results in exposure in RA subjects similar to that expected from healthy volunteers and asthmatics.

Enrollment

6 patients

Sex

All

Ages

50+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

No clinically significant disease as determined by history, physical examination and screening investigations.
RA subjects on methotrexate (7.5mg - 25mg per week)
Body weight >50 kg for males and >45 kg for females, who are not morbidly obese
Diagnosis of RA
Active disease defined as DAS28 = 4.0 and at least one MCP joint with either detectable vascularity or thickness
Stable doses of DMARDs (Disease-modifying anti-rheumatic drugs, which must include methotrexate and can also include but is not restricted to sulphasalazine and hydroxychloroquine in any combination) for 8 weeks prior to enrolment
Must be on stable folate supplements
Subjects using NSAIDs or Cox-2 inhibitors must have been on stable doses for 2 weeks prior to screening
LFT functions (ALT, AST, ALP) = 1.5 x ULN at screening and which have been stable on at least 2 occasions in the 7 months prior to screening
Must provide signed and dated written informed consent prior to admission to the study
Ability to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion criteria

Past or present disease, which as judged by the investigator, may affect the outcome of this study.
Clinically significant abnormalities in safety laboratory analysis at screening
Pregnant or nursing women
Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception as outlined
As a result of the medical interview, physical examination or screening investigations, the Physician Responsible considers the subject unfit for the study
Taking >10mg/day oral glucocorticoids
Currently receiving anti-rheumatic biological therapy
Received their final dose of infliximab or adalimumab within 3 months of enrollment
Received their final dose of etanercept or anakinra within 1 month of enrollment
Has received an investigational drug or participated in any other NCE research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to enrol.ment
Regularly drinks more than 28 units of alcohol in a week if male, or 21 units per week if female.
Has a screening QTc value of >430msec (males) or >450msec (females), PR interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements
History of liver or renal disease in the 6 months prior to screening
Current renal insufficiency (subject must have an estimated creatinine clearance less than50mL/min as estimated from the serum creatinine using the Cockroft-Gault formula
Has donated a unit of blood within the previous month or intends to donate in the month after completing the study
Has a history or drug or other allergy, which in the opinion of the physician responsible, contraindicates their participation
History of, or risk factors for, HIV, Hepatitis B and Hepatitis C
History of drug abuse