Introduction Treatment of severe chronic constipation (CC) is suboptimal. Prucalopride (PRU) is a selective high affinity 5-HT4 receptor agonist, first representative of new chemical class (dihydro-benzofurancarboxamide compounds), developed for CC treatment. This study evaluates the combined efficacy results of PRU in 3 identical pivotal, randomised, placebo (PLA)-controlled trials. The objective of each trial was to compare the efficacy and safety of a 12-week once daily treatment of 2 or 4 mg PRU with PLA in CC.
Methods All 3 trials, 2 in USA and one in Europe, Canada, Australia and South Africa, were of identical design with 3 parallel treatment groups: PLA, PRU 2 mg and PRU 4 mg. A 12-week treatment phase followed a 2-week run-in. For research purposes a most stringent primary end point was selected: the % of patients with an average of ≥3 spontaneous complete bowel movements (SCBM) per week over a 12-week treatment period (ie, normalisation of bowel movements). Clinical benefit could also be present in patients who did not meet this criterion but satisfied other efficacy end points. Patients' best response was derived from (in order of importance): an average increase of ≥ 1 SCBM/week, an improvement of ≥ 1 point on a satisfaction scale (validated PAC-QOL 5-point subscale), an increase of ≥ 1 SBM or an increase of ≥ 1 BM.
Results A total of 1924 ITT patients were included; 89% female, average age 47 years, average duration of constipation 20 years. During the 2-week run-in 57% of the patients had no SCBM. In each individual trial the results for the primary and secondary end points were significantly better for both PRU groups compared to PLA.
Thus, in addition to the response on the primary end point almost 75% of patients had clinical benefit from treatment with PRU with at least an increase of ≥ 1 SBM.
Conclusion In addition to primary response rates of about 24% with both 2 and 4 mg PRU, another 50% of patients had clinical benefit of at least an increase of ≥ 1 SBM per week.
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Competing interests V. Stanghellini Consultant for: Movetis NV, L. Vandeplassche Employee of: Movetis NV, R. Kerstens Employee of: Movetis NV.