Background : Prucalopride (PR) is a novel 5‐HT4 agonist enterokinetic compound. Aim : To evaluate its effect on bowel function, gut transit and anorectal function in healthy volunteers using a double‐blind, placebo‐controlled crossover study. Methods : Twenty‐four healthy volunteers (12 men, 12 women, mean age 25 years, range 20–53 years) were randomly assigned to 1 mg/placebo or 2 mg/placebo (PL). The trial consisted of five consecutive 1 week periods: no drug treatment, PR treatment or PL, washout, PL or PR, no treatment. Subjects maintained a diary of bowel function during the entire study period. Total intestinal transit time (TITT), mean colonic transit time (MCTT) and anorectal function (anal manometry, rectal sensitivity and rectal compliance) were assessed at the end of both treatment periods. Electrocardiography and blood sampling were performed for safety analysis; blood sampling was also used to check compliance. Results : No subjects withdrew from the study. Treatment with PR 2 mg showed a statistically significant increase in mean number of weekly stools (11.5 vs. 7.1 compared to PL, P = 0.04) and in the percentage of loose/watery stools (48 vs. 12% compared to PL, P = 0.005). Within 1 week, stool frequency and consistency returned to baseline values when treatment was stopped. MCTT was shortened significantly with both doses, i.e. from 35 h on PL to 25 h on PR 1 mg (P = 0.01) and from 43 h on PL to 22 h on PR 2 mg (P = 0.02). Anorectal function was unaffected by PR. Transient and moderate headache occurred in nine subjects during PR treatment and in six subjects during PL treatment. Conclusion : Prucalopride is well tolerated by healthy subjects and has a marked and consistent effect on stool frequency and consistency, and on colonic transit. In the present study prucalopride did not affect visceral sensitivity or sphincter function. It holds promise for patients with slow transit constipation.

Objective: The aim of this study was to assess patient preference in terms of quality of life (QoL), analgesia and bowel function for patients with moderate to severe chronic non-malignant pain, when treated with oxycodone PR/naloxone PR compared with the previous WHO-step I and/or WHO-step II analgesic treatment . Study design: This was a 3-week open-label phase 3b study conducted in Belgium and the Netherlands, after 3 weeks patients could enter an extension phase. Patient preference with respect to QoL for oxycodone PR/naloxone PR treatment compared with previous WHO-step I and/or WHO-step II analgesics was assessed. A patient was considered a responder with respect to QoL if this assessment was 'better' or 'much better' compared with previous WHO-step I or II analgesics at any time point. Results: Response rate with respect to QoL was 59.2% (95% CI: 51.7-66.8%) for the Full Analysis (FA)-population, for the Per Protocol-population response rate was 71.7% (95% CI: 63.1-80.3%). Explorative analysis showed that response rate with respect to QoL was highest in constipated patients pretreated with WHO-step II analgesics (73.8%). Mean AE SD pain score in the FA-population at start was 74.7 AE 16.6 decreasing to 53.9 AE 24.3 after a median (range) treatment period of 173.5 (31-771) days. For constipated subjects the significant reduction in constipation [improvement of the Bowel Function Index (BFI)], was À24.8 points (95% CI: À17.1 to À32.5). BFI for non-constipated subjects remained well below 28.8. Adverse events with oxycodone PR/naloxone PR treatment were well-known opioid-related adverse events. Conclusion: This study shows that the studied patients previously treated with WHO-step I and/or WHOstep II analgesics prefer treatment with oxycodone PR/naloxone PR with respect to QoL. Moreover, the study shows that treatment with oxycodone PR/naloxone PR significantly reduces OIC in constipated patients and that non-constipated patients do not develop OIC during treatment with oxycodone PR/naloxone PR. What's knownOxycodone PR/Naloxone PR improves bowel function without affecting analgesia in patients treated with WHO-step III analgesics and symptoms of OIC. What's newPatients previously treated with WHO-step I and/or WHO-step II analgesics prefer treatment with oxycodone PR/naloxone PR with respect to quality of life. Oxycodone PR/Naloxone PR prevents OIC in nonconstipated subjects and improves OIC in constipated subjects even after previous treatment with WHOstep I and/or WHO-step II analgesics.