K(D)PT showed marked anti-inflammatory properties in preclinical studies and exhibited very low toxicity in phase I and preclinical trials. In this study, efficacy and safety of oral K(D)PT were evaluated in patients with mild-to-moderate active ulcerative colitis.Methods:
A multicenter, randomized, double-blind, phase IIa trial was performed comparing add-on oral K(D)PT twice a day (20, 50, or 100 mg) with placebo in patients with mild-to-moderate active ulcerative colitis on baseline medication. The primary objective was to determine the difference in time to sustained improvement in colitis activity index (CAI) of ≥50% at week 8 between pooled K(D)PT group and placebo. Secondary endpoints included remission rates and CAI response at different time points.Results:
Compared with placebo, K(D)PT (pooled group) resulted in significantly higher proportions of patients in remission at 2 and 4 weeks, (2 wk: P = 0.0349; 4 wk: P = 0.0278) and a significantly higher proportion of patients with CAI response at week 8 (P = 0.0434). K(D)PT (pooled group) met the primary endpoint after additional analyses. Because of high placebo response rates, subgroup analyses tried to identify patients with unquestionably active and more severe, but still moderate, disease (CAI score ≥9 or taking more than one concomitant medication). These subgroups showed earlier and statistically significant CAI responses to K(D)PT versus placebo. All doses of K(D)PT were well tolerated.Conclusions:
Despite a very high placebo rate after week 4, study data in this preliminary trial strongly suggest that add-on K(D)PT is efficacious in patients with mild-to-moderate ulcerative colitis. Moreover, K(D)PT showed an excellent safety profile.