Efficacy and safety of a crystalline lactulose preparation (SK-1202) in Japanese patients with chronic constipation: a randomized, double-blind, placebo-controlled, dose-finding study.

BACKGROUND: Clinical evidence of lactulose for chronic constipation in Japan was lacking. We performed a randomized, double-blind, placebo-controlled, dose-finding study in Japanese patients with chronic constipation to estimate the optimal clinical dose of lactulose. METHODS: Overall, 250 patients were randomized to receive SK-1202 (13, 26, or 39 g/day, as crystalline lactulose dosage) or placebo twice daily (morning and evening) orally for 2 weeks. The primary endpoint was the change from baseline frequency of spontaneous bowel movements (SBMs) at Week 1. The secondary endpoints included the change from baseline of SBMs at Week 2, percentage of patients experiencing SBM within 24 and/or 48 h of the initial dose, stool consistency, and constipation severity, and adverse events were also evaluated. RESULTS: The 26 and 39 g/day of SK-1202 induced significantly and dose-dependently more increase in SBM at Week 1 than placebo (p = 0.003, p < 0.001). These groups also showed significant improvements in the secondary endpoints. There were no significant differences in the incidence of adverse drug reactions (ADRs) between the placebo and SK-1202 groups. Gastrointestinal disorder was the most common ADR, and diarrhea developed in 6 patients (9.7%) treated with 39 g/day; however, the symptoms were mild in severity and resolved after follow-up, dose reduction, or dose suspension. SK-1202 was generally well tolerated up to 39 g/day. CONCLUSION: Our results suggest that SK-1202 is useful in Japanese patients with chronic constipation, and optimal dose of SK-1202 is 26 g/day.