UNASSIGNED: A previous phase 3 trial of prucalopride in pediatric patients (6 months-18 years old) with functional constipation (FC) demonstrated no efficacy versus placebo. We designed an additional phase 3 trial to further assess the efficacy, long-term safety and tolerability of prucalopride in children and adolescents.
UNASSIGNED: This multicenter trial (ClinicalTrials.gov identifier: NCT04759833; EudraCT number: 2022-003221-22) comprises a 12-week, randomized, double-blind, placebo-controlled phase, followed by a 36-week, double-blind, safety extension phase. Approximately 240 toilet-trained patients aged 3-17 years will be randomized 1:1:1 to receive low- (0.04 mg/kg) or high-dose (0.08 mg/kg) prucalopride, or placebo once daily. Fifteen non-toilet-trained patients ≥6 months old with FC will be included in an exploratory efficacy and safety analysis.
UNASSIGNED: The efficacy endpoints used in this study will differ from those used in adults and in the previous pediatric phase 3 trial; they have been adapted to be more suitable for a wider age range of pediatric patients. Both study phases will be longer than in the previous pediatric study, providing a longer time period in which to assess the efficacy and safety of prucalopride. Study participants will be identified using the modified Rome IV criteria for FC, instead of the Rome III criteria, and non-toilet-trained patients will be included, which will broaden the population of pediatric patients assessed. Patients will undergo fecal disimpaction before randomization and undergo standardized continuous behavioral therapy throughout the trial. This pediatric study of prucalopride will aim to demonstrate the efficacy and long-term safety of this treatment.

Chronic constipation (CC), a common functional gastrointestinal disorder, has laxatives as its mainstay of treatment. Refractoriness to laxatives calls for better treatment options. Prucalopride is a novel, well-tolerated enterokinetic with high 5-hydroxytryptamine 4 receptor selectivity. This study was undertaken with the intention to establish the efficacy and safety of prucalopride with placebo in adults with refractory CC.
Patients were screened and 180 patients fulfilling the inclusion criteria were simply randomized into 2 groups either to receive prucalopride 2 mg (n = 90) or placebo (n = 90) once daily for a duration of 12 weeks. The efficacy endpoints (primary) were intended to measure the proportion of patients with three or more spontaneous complete bowel movements (SCBMs) per week over 12 weeks. Secondary endpoints were assessed via the validated questionnaires. Adverse events, electrocardiogram, and other laboratory parameters were monitored at different time intervals.
Efficacy and safety were analyzed in 180 patients simply randomized (1:1) into group A (prucalopride arm, n = 90) and group B (placebo arm, n = 90). Patients having three or more SCBMs per week in the prucalopride arm (2 mg) were 41% as against to 12% in the placebo arm (P < 0.001). A significant increase (P < 0.001) in the number of spontaneous bowel movements per week plus an increase of average bowel movement by 1 point per week was seen in the prucalopride arm. Secondary efficacy endpoints which included patients\' treatment satisfaction, improvement in the perception of constipation symptoms using the patient assessment of constipation -symptoms and stool consistency score changes were more pronounced in the prucalopride arm than the placebo. The most common adverse events reported from both the groups were headache, nausea, bloating, and diarrhea. No significant cardiovascular changes or laboratory abnormality was detected throughout the study period.
Prucalopride is effective in laxative refractory CC cases with a good safety profile.

Polyethylene glycol (PEG), bisacodyl, and prucalopride have been reported to be more effective than placebo in treating patients with constipation but about 50% of the patients still do not respond to these medications. Only bisacodyl and prucalopride are expected to directly stimulate the colonic motility in humans in vivo. As no previous study has done this, the aim of the study was to investigate the effect of PEG, bisacodyl, and prucalopride as compared to placebo on colonic motility assessed by means of the high-resolution manometry (HRM) in healthy subjects.
Ten healthy subjects have been enrolled in an acute, open label, randomized, reader-blinded, crossover study and requested to undergo a colonoscopy-assisted HRM measuring their colonic motility before and after oral administration of 13.8 g (two doses) PEG, 10 mg bisacodyl, 2 mg prucalopride, and placebo.
In the human prepared colon, oral administration of PEG significantly increases the number of low-amplitude long distance propagating contractions (p = 0.007 vs placebo) while bisacodyl significantly increases the number of high-amplitude propagating contractions (HAPCs) (all p < 0.01 vs PEG, prucalopride, and placebo). Prucalopride has no major effect on the number of propagating contractions but increases HAPCs amplitude (p = 0.01).
In humans, PEG, prucalopride, and bisacodyl have distinct effects on colonic motility. This information has clinical implication, as it indicates that the combination of prucalopride and bisacodyl, normally not considered in clinical practice, could be effective in treating patients with constipation refractory to single medications.

Clozapine remains as the gold standard for the management of treatment resistant schizophrenia. Nevertheless, mortality and morbidity associated with Clozapine is partly contributed by its adverse effect of constipation in view of its prominent anticholinergic properties. Despite the evidence that approximately 60% of patients on Clozapine will experience constipation, there is no proper guideline as to the best laxative in the treatment of Clozapine induced constipation. Hence this study was conducted to evaluate the efficacy and safety of Prucalopride and Lactulose in the treatment of Clozapine induced constipation. This was a four week, prospective, open-label head to head comparison study between Prucalopride and Lactulose in the treatment of Clozapine induced constipation. Male and female patients on Clozapine between the age of 18-60 with an established diagnosis of treatment resistant schizophrenia with ≤2 spontaneous complete bowel movement per week were recruited in this study. Eligible patients were assigned into two groups. Patients received Prucalopride 2 mg once daily or Lactulose 10 g once daily for four weeks. Efficacy was analyzed in 58 patients. The proportion of patient with ≥3 spontaneous complete bowel movement (SCBM) was higher in the Prucalopride 2 mg group, reaching significance at Week 4 with p-value of (p = 0.029). The proportion of patient with ≥3 SCBM at Week 1 was 71.4% in the Prucalopride 2 mg group and 60% in the Lactulose 10 g group. The proportion of patient with ≥3 SCBM at Week 4 was 85.7% in the Prucalopride 2 mg group and the proportion remained at 60% in the Lactulose 10 g group. The improvement in the dissatisfaction and treatment satisfaction subscales of the patient assessment of constipation-quality of life (PAC-QOL) were higher in the Prucalopride 2 mg group compared to the Lactulose 10 g group. The common adverse events associated with Prucalopride 2 mg were abdominal pain and loose stools which was transient and subsided within a few days. Over four weeks, in this population of patients with Clozapine induced constipation, Prucalopride 2 mg significantly improved the bowel movement and it was safe.

Gastroparesis, defined by delayed gastric emptying in the absence of mechanical outlet obstruction, is a frequent neuropathic complication of diabetes mellitus, and effective treatments are lacking. Prucalopride is a pan-gut prokinetic with selective agonist effects on serotonin 5-HT4 receptors in the gut. This study aimed to assess the effect of prucalopride 4 mg daily on Gastroparesis Cardinal Symptom Index (GCSI), meal-related symptom score (MRSS), and gastric emptying rate in diabetic or connective tissue disease (CTD)-related gastroparesis patients.
This was a double-blind crossover trial of four-week treatment periods with prucalopride or placebo divided by two weeks of washout. GSCI, MRSS, gastric emptying scintigraphy, PAGI-SYM, and PAGI-QoL were assessed at baseline and the end of each treatment period. Daily bowel movement (BM) frequency and gastrointestinal symptoms were recorded in each period.
Fifteen gastroparesis patients (13 diabetic, 2 CTD) were enrolled. GCSI scores were lower than baseline but not different between treatment arms. MRSS scores over time or cumulative score were not significantly different between groups. Gastric emptying was more rapid in the prucalopride treatment period, with mean four-hour meal retention of 22 ± 6% in PRU period vs 40 ± 9% in the placebo period (P = 0.05). Weekly BM frequency was significantly higher in prucalopride than placebo periods (10.5 ± 1.8 vs 7.5 ± 0.8, P < 0.0001). Perception of weight loss was higher in patients on prucalopride. Analysis of diabetic gastroparesis (n = 13) population did not change the conclusions.
Prucalopride at 4 mg accelerates gastric emptying and bowel movement frequency but does not appear to ameliorate gastroparesis or meal-related symptoms in this study.

OBJECTIVE: Paralytic ileus is a common intestinal dysfunction in critically ill patients, which results in complications and poor hospital outcomes. There are still no established effective medications, except correcting the primary causes and prokinetics trial, which have limited efficacy and potential adverse events. This study aims to evaluate the efficacy of prucalopride on paralytic ileus in critically ill patients.
METHODS: A randomized, double-blind, placebo-controlled trial of five consecutive days treatment periods was conducted. Critically ill patients with paralytic ileus were included. The primary endpoint was the improvement of bowel dilatation on plain abdominal radiography. The secondary endpoint was the change of abdominal circumference.
RESULTS: Twenty patients were consecutively enrolled in the study. There was no significant difference in baseline characteristics of patients. The common causes of hospitalization were infection and respiratory problems. The maximum large bowel diameters dramatically decreased in prucalopride group and reached maximum point on the third day after intervention when compared with placebo (-2.1 [± 1.8] vs 0.3 [± 1.5] cm, P = 0.01). The maximum small bowel diameters were noticeably less decreased and were not significantly different when compared with placebo. The abdominal circumferences notably decreased and significantly diverged from placebo on the third day.
CONCLUSIONS: Prucalopride was an effective enterokinetic agent to improve non-severe inflammatory/ischemic bowel conditions related paralytic ileus in critically ill patients. Its effect was predominant on large intestine but could not be well demonstrated on small bowel in this study. Future study or concomitant other prokinetics for upper gut motility should be further evaluated.

OBJECTIVE: Sodium phosphate solution (NaP) in oral form is well known and frequently used for good quality bowel cleansing before a colonoscopy, but it carries the potential risk of electrolyte disturbance and dehydration. Prucalopride mitigates severe constipation by promoting colon motility. We evaluated the hypothesis that prucalopride plus one single dose of 45 mL NaP could be used as an alternative bowel preparation.
METHODS: Consenting adult patients undergoing a screening colonoscopy were randomized to receive 90 mL NaP (90-NaP) in two split doses or prucalopride 2 mg plus 45 mL NaP (P-NaP). Patients completed a questionnaire about adverse gastrointestinal symptoms and acceptability for bowel preparation. The effectiveness of colon preparation was evaluated according to the Ottawa bowel preparation scale.
RESULTS: Bowel cleansing was achieved in 92 patients with 90-NaP and in 97 patients with P-NaP. There was no significant difference in bowel cleansing level and adverse gastrointestinal symptoms between the two groups. However, more patients in the P-NaP group were willing to undertake the same regimen for a subsequent colonoscopy bowel preparation than those in 90-NaP group (82/97; 85% vs 51/92; 55%, P < 0.001).
CONCLUSIONS: The combination of 2 mg prucalopride and 45 mL NaP appeared to provide the same level of bowel cleansing, but it was more acceptable than the 90 mL NaP in split doses.

OBJECTIVE: Bowel cleansing is a major patient complaint during colonoscopy. Adding laxatives to the bowel preparation is effective in replacing a portion of bowel preparation solution and reducing its volume. Prucalopride is a serotonin receptor agonist that stimulates gastrointestinal motility and provides propulsive force for defecation. This study aimed to compare 1 L polyethylene glycol (PEG) with ascorbic acid (Asc) plus 2 mg prucalopride (1LP/AP) and 2 L PEG with Asc (2LP/A) for colonoscopy preparation with respect to bowel-cleansing quality and side effects.
METHODS: A single-center, randomized, prospective study was conducted with 260 outpatients administered either 1LP/AP or 2LP/A. The primary endpoint was bowel preparation quality, which was evaluated using the Boston Bowel Preparation Scale and Aronchick Bowel Preparation Scale, and the secondary endpoints were patient tolerability and acceptability, assessed by a questionnaire-based survey.
RESULTS: The adequate bowel preparation rates were 88.5% and 83.1% in the 2LP/A and 1LP/AP groups, respectively, and the efficacy of 1LP/AP was equivalent to the control regimen (p=.216). Other colonoscopic variables including adenoma detection rate were similar in both groups. Patient tolerability and acceptability were not significantly different, but patients in the 1LP/AP group were more willing to repeat the same regimen (p=.039).
CONCLUSIONS: Bowel preparation quality with 1LP/AP was equivalent to that with 2LP/A, which did not increase the occurrence of side effects, but it reduced the volume of the solution ingested, and increased patient satisfaction.

Colonoscopy is a crucial diagnostic instrument for colorectal cancer screening and an adequate bowel preparation is definitely decisive for the success of the procedure. Especially in elderly patients, bowel cleansing is considered a big issue, because it is often poorly tolerated for many reasons (like inability to swallow large volume of liquids or unlikable taste); this can cause a suboptimal preparation that may lead to miss a neoplastic lesion. There is relatively little data about how to improve preparation tolerability. The purpose of our pilot study was to analyze the effect of prucalopride (Resolor®), a highly selective serotonin 5HT4 receptor agonist used for chronic constipation for its ability to stimulate gastrointestinal peristalsis, undertaken the day before colonoscopy, followed by half volume of polyethylene glycol solution. We found that this can be a good and safe method to achieve an adequate and better-tolerated colon cleansing.

Chronic constipation is a prevalent gastrointestinal disorder globally. It is often treated with medications such as laxatives. Newer therapies to improve gastric motility include the selective 5-hydroxytryptamine receptor-4 agonist prucalopride, which is licensed for the treatment of chronic constipation in adults. The aim of this study was to investigate the pharmacokinetic properties and excretion of prucalopride in healthy individuals, using a microtracer approach with (14)C radioactivity detection using liquid scintillation counting and accelerator mass spectrometry.
This was a single-period, open-label, nonrandomized absorption, metabolism, and excretion study of [(14)C]prucalopride. Participants were 6 healthy men aged 18 to 50 years. After screening, participants were administered a single dose of [(14)C]prucalopride succinate 2 mg (~200 nCi). Postadministration, urine, feces, and blood samples were collected over a 10-day period. Safety and adverse event data were also collected.
Almost 100% of the administered dose of radioactivity was recovered, with a mean (SD) of 84.2% (8.88%) recovered in urine and 13.3% (1.73%) recovered in feces. The mean blood-to-plasma concentration ratio of 1.9 indicated uptake of prucalopride into blood cells. The renal clearance of prucalopride was 17.0 (2.5) L/h, which is higher than the glomerular filtration rate in healthy individuals, suggesting active renal transport of prucalopride. Prucalopride was well tolerated, with no serious adverse events reported.
Prucalopride was well absorbed and excreted mainly by the kidneys, including both passive and active transporter mechanisms. Quantitative recovery of the radioactive dose was achieved. Consistent with previous studies, prucalopride was generally well tolerated. ClinicalTrials.gov identifier: NCT01807000.