Mean compliance was 95.50% in the ITT set [standard deviation (SD) = 10.05] and 94.66% in the placebo group (SD = 13.73). During the study, the body weight of the patients remained constant in both groups (Fig. 2). The overall sum score of liver histology between the UDCA and placebo groups did not change significantly in the ITT set or in the PP set (PP set not shown), regardless of whether the modified Brunt score or NAS was applied (Table 4). There was a placebo effect shown by the decrease in the sum score in the placebo group. Accordingly, the primary endpoint of the study was not achieved. Of the single variables, Forskolin clinical trial only lobular inflammation improved when the modified Brunt score and NAS were applied (Table 4).

Staging had not changed at 18 months from the baseline in the UDCA and placebo groups (P for the ITT set = 0.133; PP set not shown; Table 4). In subgroup analyses of the secondary variables in UDCA-treated patients (ITT and PP sets), significant improvement in lobular inflammation in comparison with placebo-treated patients could be allocated to males (P < 0.011), patients ≤50 years old (P < 0.002), patients with a BMI ≤30 kg/m2 (P < 0.023), patients with find protocol a blood pressure ≥130/85 mm Hg (P < 0.018), patients with a histology sum score >7 (P < 0.005), patients with an ALT level ≥ 80 U/L at the baseline (P < 0.025), and patients in whom

the decrease in ALT after 18 months of therapy was at least 50% of the baseline (P < 0.004). In patients with a BMI ≤30 kg/m2, centrilobular fibrosis also improved significantly (P < 0.046; PP set not shown). In patients of the placebo group in whom the ALT level after 18 months had dropped by at least 50%, lobular inflammation was just below significance

(P = 0.07). During therapy, levels of AST, ALT, alkaline phosphatase (AP), and γ-glutamyl transferase (GGT) improved in both treatment groups, MCE公司 but differences between the two treatment groups were not significant, except for GGT (Table 5). Subgroup analyses did not provide any significant differences (data not shown). The sum score of symptoms was not different between the two study groups at the baseline and at the end of the study. In both groups, symptoms revealed a numerical decrease over the study period. Subgroup analyses showed that only in patients with a BMI ≤30 kg/m2 did right upper quadrant abdominal discomfort improve significantly (P < 0.032) in the PP set. No safety issues were raised during this long-term study with the high dose of UDCA. A total of 28 adverse drug reactions were reported in 21 patients; 16 adverse drug reactions occurred in the UDCA group, and 12 occurred in the placebo group. Diarrhea was the predominant reaction in the UDCA group and occurred more often in comparison with the placebo group (11 events versus 1 event). All reactions except one (fatigue in the UDCA group) were documented with mild or moderate intensity, and all reactions were transient.