Descriptive statistical methods were used to summarize all primary and secondary efficacy the site variables. Inhibitors,Modulators,Libraries Significance tests were carried out at the 2 sided 5% level. Changes from baseline in tender joint count, swollen joint count, patients pain assessment, patients and physicians global assessment, CRP, ESR, HAQ DI and MAF were compared between treatment groups. If the assumption of normality was not satisfied for these data, then the data were transformed prior to analysis. Weighted mean DAS28 score The weighted DAS28 was defined by the area under the curve divided by the number of days. The weighted mean DAS28 was calculated and summary statistics are presented for Parts Inhibitors,Modulators,Libraries A, B and C. The difference in the mean of the two treatment groups is presented together with the corresponding 2 sided 95% confidence interval and the 2 sided P value.

For EULAR, ACR20, ACR50 and ACR70 response rates, the Cochran Mantel Haenszel test was used for comparing the responder rates at each visit for GSK315234A versus placebo stratified by subgroup factors. Results In total, 135 patients with RA were dosed. Their demographic details are given in Table 1. All patients in Part A completed the study. Three patients in Part B withdrew due Inhibitors,Modulators,Libraries to lack of efficacy, investigator discretion and patient withdrawing consent. One patient in Part C who received one dose of treatment had to be withdrawn from the study and ana lysis due to protocol violation. Efficacy In Part A, there was a statistically significant difference in DAS28 between 3 mg kg and placebo at Days 56, 84 and 91.

There was a statistically significant difference between 0. 3 mg kg, 3 mg kg and 10 mg kg compared to placebo, at Day 84. The largest adjusted mean change in DAS28 from baseline was observed for the 3 mg kg group at Day 84 and the difference, compared to placebo, was ?1. 43. For Part B, no significant difference was observed bet ween 6 mg kg and placebo. For Part C, a statistically Inhibitors,Modulators,Libraries sig nificant difference was observed at Days 40, 84 and 100 between the 500 mg SC group compared to placebo. Figure 2 shows the changes in DAS28 with time in parts A, B and C. No significant findings were observed at any of the time points for EULAR response criteria, DAS28 remis sion, ACR20, ACR50 or ACR70. For swollen joint count, a statistically significant bene fit for the comparison of GSK315234 versus placebo was observed for the 0.

3 mg kg, 3 mg kg and 10 mg Inhibitors,Modulators,Libraries kg dose groups at various time points in Part A. There was no statistically significant improvement of 6 mg kg over pla cebo at any time point in Part B. No statistically significant improvement in HAQ DI compared to placebo was observed http://www.selleckchem.com/products/Tipifarnib(R115777).html at any time point for all treatment groups. For both ESR and CRP, there was no statistically significant improvement with GSK315234 compared placebo at any time point after the 24 hour time point in Parts A, B and C.