Objective: We aimed to determine the efficacy, impact on quality of life (QOL), and safety of prucalopride, a selective, high-affinity 5-HT4 receptor agonist, in patients with chronic constipation (CC).
Methods: In this multi-centre, randomized, placebo-controlled, parallel-group, phase III study, patients with CC (≤2 spontaneous complete bowel movements ([SCBM]/week) received 2 or 4 mg prucalopride or placebo, once daily, for 12 weeks. The primary efficacy endpoint was the proportion of patients reaching ≥3 SCBM/week. The key secondary efficacy endpoint was the proportion of patients having an increase of ≥1 SCBM/week. The primary QOL endpoint was the Patient Assessment of Constipation (PAC)-QOL satisfaction subscale score. Safety parameters included adverse events, laboratory values, and cardiovascular events.
Results: Efficacy was evaluated over 713 patients. Averaged over 12 weeks, higher proportions of patients on prucalopride 2 mg (19.5%; p<0.01), 4 mg (23.6%; p<0.001) had ≥3 SCBM/week (or normalization of bowel function) compared with placebo (9.6%). Similar results were seen in the subgroup (83%) of patients dissatisfied with previous laxative treatment. Both doses of prucalopride also significantly improved secondary efficacy and QOL endpoints, including the proportion of patients with an increase of ≥1 SCBM/week, evacuation completeness, perceived disease severity and treatment effectiveness, and QOL. Prucalopride 4 mg significantly reduced the need for straining versus placebo (p<0.05). The most frequent treatment-related adverse events were headache and diarrhoea. Both doses of prucalopride were safe and well-tolerated.
Conclusion: Prucalopride significantly and consistently improved bowel function, associated symptoms and satisfaction in chronically constipated patients.