−0.3 ± 21.1 mmHg (n = 59); P = 0.6963; change in DBP from baseline to the final visit: −2.5 ± 10.3 mmHg (n = 62) vs. −2.7 ± 12.3 mmHg (n = 59); P = 0.9058) (Table 2). Table 2 Systolic and diastolic blood pressure levels at the baseline and during follow-up (intent-to-treat population)   SBP (mmHg) DBP (mmHg) Topiroxostat Placebo Topiroxostat check details Placebo Baseline 135.2 ± 17.3 (62) 134.6 ± 20.0 (59) 84.8 ± 11.8 (62) 84.1 ± 11.6 (59) Week 2 134.2 ± 18.3 (60) 136.3 ± 21.0 (59) 84.8 ± 11.9 (60) 83.7 ± 11.7 (59) Week 6 133.3 ± 18.0 (60) 132.5 ± 20.8 (60) 84.3 ± 10.7 (60) 82.8 ± 12.4 (60) Week 10 132.1 ± 16.4 (60) 134.1 ± 22.3 (57) 82.8 ± 11.8 (60) 82.2 ± 12.9 (57) Week 14 131.9 ± 19.5 (59) 131.3 ± 20.0 (55) 82.6 ± 11.5

(59) 80.5 ± 10.4 (55) Week 18 131.5 ± 18.4 (58) 131.6 ± 20.3 (54) 81.6 ± 11.1 (58) 80.2 ± 10.9 (54) Week 22 133.6 ± 17.8 (56) 133.8 ± 21.2 (55) 81.7 ± 11.6 (56) 80.9 ± 10.4 (55) Mean ± SD (n) SBP systolic blood pressure, DBP diastolic blood pressure Serum adiponectin The percent change of the serum adiponectin level from the baseline to the final visit tended to be higher in the topiroxostat group, although the difference was not statistically

significant (Topiroxostat: 3.9 %; 95 % CI −1.2 to 9.2 %, Placebo: −0.1 %, 95 % CI, −4.5 to 4.5 %; P = 0.2454). Safety All AEs were designated and classified as mild to severe in terms of the severity by individual investigators, and their buy INCB28060 causal relationships with the study drug were evaluated. There were no deaths reported during the study. Thymidylate synthase Serious AEs were reported in 2 patients (4 cases) from the topiroxostat group and 2 patients (2 cases) from the placebo group. In detail, “Polyarthritis (n = 1)” in the topiroxostat group, and “Acute hepatitis (n = 1)” in the placebo group were considered by the investigator to be related to the study drug, and patients with these AEs were withdrawn from the study. The AEs that led to treatment withdrawal were “ALT, AST increased (n = 1)”, “Eczema (n = 1)”, and “Polyarthritis (n = 1)” in the topiroxostat group, and “Acute hepatitis (n = 1)” in the placebo group. Overall, the rate of AEs was similar in the two groups and the frequently reported AEs (≥5 %) are listed

in Table 3. All of the AEs were mild to moderate in severity. The incidence of ‘alanine aminotransferase (ALT) increased’ was higher in the topiroxostat group than that in the placebo group. In detail, the incidence of concurrent increase of the total bilirubin or alkaline phosphatase with the ALT was similar in both groups (Table 4). Table 3 Summary of adverse events occurring in ≥5 % of patients in either treatment group (safety population) AE Number (%) of patients Topiroxostat (n = 62) Placebo (n = 60) Any AEs 42 (67.7) 41 (68.3) Nasopharyngitis 13 (21.0) 13 (21.7) Conjunctivitis allergic 1 (1.6) 4 (6.7) Rhinitis allergic 1 (1.6) 4 (6.