Rheumatoid arthritis MedDRA version: 12.0 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: GSK706769
Product Code: GSK706769
Pharmaceutical Form: Film-coated tablet
CAS Number: 880356-67-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female over 18 years of age, at the time of signing the informed consent. 2. A female subject is eligible to participate if she is of child-bearing potential (with negative serum pregnancy test at screening and negative urine pregnancy test within 24 hours prior to the first dose of investigational product, with confirmation by serum testing within 24 hours after first dose) and agrees to use one of the contraception methods listed in Section 8.1 of the protocol for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 4 days post-last dose. 3. Body weight = 50 kg and BMI within the range 19 – 32 kg/m2 (inclusive). 4. The subject has a diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR) and has been treated with an anti TNF-alpha agent for 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. The subject is using oral prednisolone at doses > 10mg/day. 2. The subject’s NSAID or glucocorticoid dosing regimen has changed during the 4 weeks prior to randomisation. 3. The subject is receiving DMARDs other than Enbrel and methotrexate 4. The subject’s current methotrexate regimen has changed significantly (i.e. likely to impact disease activity during the study period) within the 3 months prior to dosing e.g. changes in dose of greater than 2.5mg. 5. Use of CYP3A4 inhibitors/inducers within 14 days prior to dosing and CYP3A4 substrates with a narrow therapeutic index within 7 days prior to dosing 6. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 7. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 8. Absolute neutrophil count 21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits. 15. The subject has an acute infection or a history of repeated or chronic infections 16. The subject has significant cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as a participant in this trial. 17. Subjects with autoimmune hemolytic anemia or G6PD deficiency 18. Malignancy in the past 2 years, except for adequately treated non-invasive cancers of the skin 19. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. 20. Lactating females. 21. Unwillingness or inability to follow the procedures outlined in the protocol. 22. Subject is mentally or legally incapacitated. 23. Consumption of grapefruit, grapefruit juice or grapefruit hybrids from 7 days prior to the first dose of study medication to day 28.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the ability of GSK706769 to maintain clinical remission after withdrawal of Enbrel in patients with RA, as determined by DAS28 scores;Secondary Objective: 1. To investigate the ability of GSK706769 to maintain clinical remission after withdrawal of Enbrel in patients with RA, as determined by the Patient Global Assessment scores and evidence of swollen or tender joints. 2. To investigate the time to relapse following withdrawal of Enbrel. 3. To investigate the safety and tolerability of GSK706769 following repeat dosing in RA subjects for up to 28 days. 4. To investigate the differences in rheumatological assessments, pain, fatigue and physical functioning following repeat dosing with GSK706769 for up to 28 days 5. To investigate the systemic pharmacokinetics (PK) of GSK706769, and its metabolite GSK1996847A, in RA Patients, following twice-daily administration at 100 mg (200 mg total dose) for 28 days; using a population PK approach (as feasible). 6. To measure CCR5 receptor occupancy (RO) in peripheral blood following repeat dosing with GSK706769 for up to 28 days, as feasible;Primary end point(s): Number of subjects that maintain remission on active versus placebo at Day 28 with remission defined as: • Change in DAS28 (SJC, TJC, ESR, patient’s global assessment) < 0.6 | — |
Countries
Belgium, Ireland
Outcome results
None listed