T1322 Safety and Tolerability of Prucalopride (Resolor ®) in Patients with Chronic Constipation: Pooled Data from Three Pivotal Phase III Studies

Abstract

Introduction Prucalopride (PRU) is a selective high affinity 5-HT4 agonist. Studies have shown that PRU effectively improved bowel movements in patients with chronic constipation (CC). Methods Three pivotal phase III double-blind, randomised, placebo (PLA)-controlled studies were conducted, identical in design. Trials consisted of a 2-week run-in period followed by a 12-week treatment period in which patients were randomised to once daily treatment with PRU 2 mg, PRU 4 mg or PLA. Adverse events (AEs) were reported and vital signs, laboratory and ECG were recorded at baseline, weeks 4 and 12 of treatment. Combined analyses of the three trials are presented. Results Eighty-nine percent of a total of 1977 treated subjects were female, average age was 47 years, average history of constipation was 20 years and >50% of patients reported to have no spontaneous complete bowel movements during the 2-week run-in period. PRU 2 mg, PRU 4 mg and PLA were administered to 659, 657 and 661 patients, respectively. AE incidence is summarised in Abstract 008 below. The higher incidence of headache, nausea and diarrhoea in the PRU groups can be explained by the pharmacodynamic effect of PRU and mainly occurred on the first day of treatment. Most AEs (≥5%) considered at least moderate in severity and possibly related to PRU were mainly related to the GI tract with a higher incidence in the PRU groups for nausea, diarrhoea, abdominal pain and headache ranging from 2.7% to 4.7% in PLA vs 5.1% to 11.8% in PRU 2 mg and 6.1% to 16.1% in PRU 4 mg. No deaths were reported. The only SAE reported in more than one patient was abdominoplasty for two patients in the PRU 4 mg group (not related to study medication). Most frequent AEs (≥2%) leading to discontinuation were also nausea, diarrhoea, abdominal pain and headache. No clinically relevant differences were observed between PRU and PLA in laboratory parameters, in vital signs or ECG values during the trial period (Abstract 047). Conclusion Treatment during 12 weeks with PRU 2 mg and 4 mg is safe and well tolerated by patients with CC.