Efficacy and Tolerability of Prucalopride in Patients with Constipation due to Spinal Cord Injury

Abstract

Background: Chronic constipation (CC) often occurs after spinal cord injury (SCI). Prucalopride is a novel, highly selective, specific serotonin 4 receptor agonist with enterokinetic properties. We evaluate the tolerability and pilot efficacy of prucalopride in the treatment of CC due to SCI. Methods: Double-blind, placebo-controlled, pilot, phase II, dose-escalation study. After 4 weeks' run in, patients received prucalopride 1 mg ( n = 8) or placebo ( n = 4); 11 new patients were randomized to prucalopride 2 mg ( n = 8) or placebo ( n = 3) once daily for 4 weeks. Patients recorded bowel function (diary) and assessed constipation severity and treatment efficacy (visual analogue scale (VAS) 0-100 mm). Colonic transit times were determined. Results: Compared with run in, mean changes in constipation severity (VAS) increased with placebo, but decreased with prucalopride 1 and 2 mg. The VAS score for treatment efficacy showed a clear dose response (medians 4, 52 and 73 for placebo, 1 and 2 mg, respectively). Diary data showed an improvement in average weekly frequency of all bowel movements over 4 weeks within the 2 mg group (median 0.6; 95% CI 0.2; 1.2). There was a significant reduction in median colonic transit time with 2 mg ( n = 4; -38.5 h (95% CI-80; -5)). Four patients (2 mg) reported moderate/severe abdominal pain, and two of these discontinued treatment. There were no clinically relevant effects on any of the safety parameters. Conclusion: This pilot study indicates that prucalopride can play an important role in the management of patients with CC due to SCI.