Introduction Prucalopride (PRU) is a high-affinity serotonin receptor (5-HT4) agonist approved in Europe for the symptomatic treatment of chronic constipation (CC) in women. The aim of this study was to evaluate the efficacy and safety of PRU in men with CC.
Method This was a phase 3, multicentre, parallel-group, double-blind trial (NCT01147926). Men aged ≥ 18 years with CC who had ≤ 2 spontaneous complete bowel movements (SCBMs)/week were randomised to receive placebo (PLA) or PRU 2 mg (starting dose of 1 mg for patients aged ≥ 65 years) once daily for 12 weeks. The primary endpoint was the proportion of men achieving a mean of ≥ 3 SCBMs/week over 12 weeks. Secondary endpoints included Patient Assessment of Constipation-Symptoms (PAC-SYM) and Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaire scores. Safety was assessed throughout the study.
Results Overall, 374 patients were randomised. More men in the PRU group than in the PLA group (37.9% vs. 17.7%, respectively; p < 0.0001) achieved ≥ 3 SCBMs/week, and more men receiving PRU achieved improvements of ≥ 1 SCBM/week (53.7% vs. 45.3%; p = 0.0743) and ≥ 1 SBM/week (65.5% vs. 43.1%; p < 0.0001). At the final on-treatment assessment, there was no significant difference between the PRU and PLA groups in the proportion of men with a clinically relevant improvement of ≥ 1 point in total PAC-SYM score (34.9% vs. 30.4%, respectively; p = 0.3152) or abdominal (39.1% vs. 35.1%; p = 0.4874) or rectal (34.9% vs. 29.2%; p = 0.2759) subscale scores. However, there was a significant difference in stool symptoms score (53.3% vs. 36.3%; p = 0.0005). The proportion of men with an improvement of ≥ 1 in total PAC-QOL score was higher with PRU (40.2%) than PLA (32.7%; p = 0.0755). PRU had a good safety profile and was well tolerated, consistent with previous studies. The incidences of serious adverse events and ischaemic cardiovascular adverse events were low and similar in both treatment groups.
Conclusion Results from this study demonstrate that PRU is effective, has a good safety profile and is well tolerated in men with CC, similar to the findings for women with CC.
Disclosure of interest Y. Yiannakou Grant/ Research Support from: Shire, Consultant for: Shire, M. Bouchoucha: None Declared, I. Schiefke: None Declared, H. Piessevaux Conflict with: Shire, R. Filip: None Declared, L. Gabalec: None Declared, D. Stephenson Employee of: Shire, R. Kerstens Employee of: Shire, K. Etherson Conflict with: Shire, A. Levine Employee of: Shire.