Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation - a 12-week, randomized, double-blind, placebo-controlled study

Background Chronic constipation may result in disabling symptoms, is often unsatisfactorily treated by laxatives and negatively impacts quality of life (QoL). Aim A randomized, double-blind, placebo-controlled, phase III trial to evaluate the efficacy and safety of a selective, high-affinity 5-HT4 receptor agonist, prucalopride, in patients with chronic constipation [<= 2 spontaneous complete bowel movements (SCBMs)/week]. Methods Placebo, 2 or 4 mg prucalopride was administered orally once daily, for 12 weeks. The primary efficacy endpoint was the proportion of patients with >= 3 SCBMs/week, averaged over 12 weeks. Other assessments included BM frequency, constipation-related QoL and symptoms and tolerability. Results Among 641 patients, significantly more patients taking prucalopride 2 or 4 mg (24%) than placebo (12%), achieved the primary efficacy endpoint (>= 3 SCBMs/week) or an increase of >= 1 SCBMs/week; 43% and 47% vs. 28% respectively. Prucalopride-treated patients also achieved significantly greater satisfaction with treatment and bowel function, and improved perception of constipation severity and constipation-related QoL, compared with placebo. Most frequent treatment-related adverse events were headache, abdominal pain, nausea and diarrhoea (mainly during day 1). There were no differences in comparison to placebo in the incidence of serious adverse effects or cardiovascular events. Conclusion Over 12 weeks, prucalopride was effective and well tolerated in chronic constipation.