Chronic constipation-associated symptoms in Asians and non-Asians, and effects of 12-week prucalopride treatment: A pooled analysis of 4 randomized, placebo-controlled trials

Abstract

AIM: To evaluate the efficacy of prucalopride (2 mg/day), a novel selective high-affinity 5-hydroxytryptamine type-4 receptor agonist, in relieving chronic constipation-associated symptoms in Asians and non-Asians.METHODS: This integrated analysis included pooled data from 4 phase-III,multicenter, randomized, double-blind, placebo-controlled studies (NCT00488137, NCT00483886, NCT00485940, NCT01116206) of patients treated with prucalopride 2mg and placebo. Efficacy in relieving chronic constipation-associated symptoms was evaluated based on improvements in the ‘Patient Assessment of Constipation Symptoms’ scores. Change from baseline in each symptom score was analyzed using an analysis of covariance model, with treatment, study, and baseline spontaneous bowel movement frequency as factors, and baseline value for each symptom score as covariates for each subgroup of interest: Asian and non-Asian. RESULTS: Overall, 1782 patients (26.7% Asians; 73.3% non-Asians), predominantly women (89.3%), were included. Prucalopride significantly improved bloating, hard stool, and straining (P<0.001, for all), compared with placebo (mean [standard deviation]) in Asians (bloating: -0.5 [0.73], -0.3 [0.73]; hard stool: -0.5 [0.82], -0.2 [0.77]; straining: -0.6 [0.78], -0.4 [0.75]) and non-Asians (bloating: -0.4 [0.71], -0.2 [0.67]; hard stool: -0.3 [0.78], -0.2 [0.79]; straining: -0.3 [0.71], -0.2 [0.69]) irrespective of symptom severity. However, abdominal pain was not significantly relieved in Asians (P=0.103) compared with non-Asians (P<0.001). The most common treatment-emergent adverse events were headache, nausea, diarrhea, and abdominal CONCLUSIONS: Prucalopride 2 mg/day was found to be well-tolerated and efficacious in relieving all chronic constipation-associated symptoms in both Asians and non-Asians, except for abdominal pain in Asians, over 12 weeks, regardless of their severity.