Clinical trial: the efficacy of open-label prucalopride treatment in patients with chronic constipation - follow-up of patients from the pivotal studies (original) (raw)
Alimentary Pharmacology & Therapeutics, 2009
Background Chronic constipation may result in disabling symptoms, is often unsatisfactorily treated by laxatives and negatively impacts quality of life (QoL).Aim A randomized, double-blind, placebo-controlled, phase III trial to evaluate the efficacy and safety of a selective, high-affinity 5-HT4 receptor agonist, prucalopride, in patients with chronic constipation [≤2 spontaneous complete bowel movements (SCBMs)/week].Methods Placebo, 2 or 4 mg prucalopride was administered orally once daily, for 12 weeks. The primary efficacy endpoint was the proportion of patients with ≥3 SCBMs/week, averaged over 12 weeks. Other assessments included BM frequency, constipation-related QoL and symptoms and tolerability.Results Among 641 patients, significantly more patients taking prucalopride 2 or 4 mg (24%) than placebo (12%), achieved the primary efficacy endpoint (≥3 SCBMs/week) or an increase of ≥1 SCBMs/week; 43% and 47% vs. 28% respectively. Prucalopride-treated patients also achieved significantly greater satisfaction with treatment and bowel function, and improved perception of constipation severity and constipation-related QoL, compared with placebo. Most frequent treatment-related adverse events were headache, abdominal pain, nausea and diarrhoea (mainly during day 1). There were no differences in comparison to placebo in the incidence of serious adverse effects or cardiovascular events.Conclusion Over 12 weeks, prucalopride was effective and well tolerated in chronic constipation.
Journal of neurogastroenterology and motility, 2016
This article highlights the role of prucalopride in the management of chronic constipation based upon the principles of meta-analysis using data reported in the published randomized, controlled trials. Sixteen randomized, controlled trials on 3943 patients reported the effectiveness of prucalopride in patients with chronic constipation. Prucalopride successfully increased the frequency of spontaneous bowel movements per week in all variable doses of 1 mg (standardized mean difference, 0.42 [95% CI, 0.18-0.66; P = 0.006]), 2 mg (standardized mean difference, 0.34 [95% CI, 0.11-0.56; P = 0.003]), and 4 mg (standardized mean difference, 0.33 [95% CI, 0.22-0.44; P = 0.00001]). The risks of adverse events or side effects such as headache, abdominal cramps, excessive flatulence, dizziness, diarrhoea, and rash were higher (odds ratio, 1.70 [95% CI, 1.27 to -2.27; P = 0.0004]) in prucalopride group. Prucalopride is clinically a beneficial pharmacotherapy for chronic constipation and its rou...
The American Journal of Gastroenterology, 2015
The American Journal of GASTROENTEROLOGY nature publishing group 741 FUNCTIONAL GI DISORDERS ORIGINAL CONTRIBUTIONS INTRODUCTION Constipation is a common, oft en chronic, gastrointestinal motility disorder characterized by a diversity of symptoms including bloating, straining, abdominal pain, lumpy or hard stools, sensation of incomplete evacuation, and infrequent defecation (fewer than three bowel movements per week) (1-3). Th e estimated global prevalence of chronic constipation is 14% ((ref. 4)) and it is more common in women and the elderly (5). Individual symptoms are frequently severe and can signifi cantly impair patients' health-related quality of life (HRQoL) (6) and decrease work productivity (1). Poor HRQoL in patients with constipation has been shown to be a predictor of increased health-care utilization (7).
Clinical Efficacy and Safety Profile of Prucalopride in Chronic Idiopathic Constipation
Cureus, 2019
Chronic idiopathic constipation (CIC) can be defined as bowel movements that are difficult to pass, are not occurring frequently, or have incomplete evacuation during defecation. A highfiber diet and laxatives are the commonly used treatments, but in many cases, they do not produce satisfactory results. The first line of treatment is osmotic laxatives. If there is no improvement, the second line is guanylate cyclase-C (GCC) agonists like linaclotide or prokinetic agents such as prucalopride. On December 14, 2018, the United States Food and Drug Administration (US FDA) approved prucalopride for treating chronic idiopathic constipation. Prucalopride is a prokinetic agent which works at the 5-hydroxytryptamine receptor 4 (5-HT4) as an agonist with greater receptor selectivity. Patients on prucalopride reported improved symptoms, quality of life and satisfaction. The most frequent adverse events were headaches and problems related to the gastrointestinal tract. Caution should be taken when using prucalopride in patients with impaired liver and renal function. In Canada, prucalopride has been approved for treatment of female patients with chronic idiopathic constipation who have failed therapy with at least two laxatives from different classes over a six-month period.
United European gastroenterology journal, 2013
Prucalopride is a selective, high-affinity, 5-hydroxytryptamine (serotonin) type 4 (5-HT4) receptor agonist with gastrointestinal prokinetic activities. This integrated analysis of data from three double-blind phase III trials (ClinicalTrials.gov: NCT00488137, NCT00483886, NCT00485940) compared the efficacy and safety of prucalopride 2 mg once daily in women with chronic constipation [≤2 spontaneous complete bowel movements (SCBM) per week] in whom laxatives had failed to provide adequate relief with that in the all-patient (AP) population of men and women with chronic constipation who had or had not obtained relief from laxatives. Patients received prucalopride 2 mg or placebo once-daily for 12 weeks. Efficacy endpoints included an average of ≥3 SCBM/week and average increases of ≥1 SCBM/week and ≥1 SBM/week over this period. A response on any of these three endpoints was considered to be clinically relevant, and an overall response rate was derived for patients satisfying any of t...
Effect of prucalopride on symptoms of chronic constipation
Neurogastroenterology & Motility, 2014
This study shows that 12 weeks of treatment with prucalopride 2 mg once daily is associated with significant improvements, compared with placebo, in common constipation symptoms in women in whom previous laxative treatment had failed to provide adequate relief.
Digestion, 2003
Background: Chronic constipation (CC) is common and there is a need for more effective and better-tolerated agents that normalize bowel function without affecting secretion. Prucalopride is a novel, selective serotonin 4 receptor agonist with enterokinetic properties. Aims: Pilot study to compare the efficacy and tolerability of prucalopride and placebo in patients with severe CC referred to a tertiary centre. Methods: After 4-weeks' run in, patients were randomized to 4 weeks' once daily, double-blind treatment with either prucalopride 4 mg (n = 27) or placebo (n = 26). A 50% dose reduction after 2 weeks' treatment was possible for patients with an excessive gastrointestinal response to the study medication (severe cramps, abdominal pain, and diarrhea). Patients assessed efficacy using a visual analogue scale (VAS) and recorded bowel function in daily diaries. The investigator assessed efficacy and total gut transit time (marker study). Results: Patient VAS assessment demonstrated that prucalopride was significantly more effective than placebo in softening stools, and decreasing straining and time to first stool. Prucalopride also had a positive effect on stool frequency, feeling of complete evacuation and total gut transit time, although these differences were not statistically significant compared with placebo. The most common adverse events were gastrointestinal symptoms and headache; most were mild to moderate. There were no clinically relevant effects on cardiovascular or laboratory parameters. Conclusions: Once-daily prucalopride 4 mg for 4 weeks is effective and well tolerated in patients with severe CC. It improves whole gut transit, reducing straining, softening stools and reducing time to first bowel movement.
Neurogastroenterology & Motility, 2010
Background Constipation affects up to 50% of the elderly; this study evaluates the efficacy, safety, and tolerability of the selective 5-HT 4 agonist prucalopride in chronically constipated elderly patients. Methods Three hundred chronic constipation patients aged ‡65 years were randomized to prucalopride (1, 2, or 4 mg once daily) or placebo for 4 weeks. The primary endpoint was the percentage of patients with ‡3 spontaneous complete bowel movements (SCBM) per week. Secondary endpoints included the percentage with an increase of ‡1 SCBM per week, BM frequency, constipation-related symptoms, quality of life (QoL), safety, and tolerability. Key Results More patients achieved ‡3 SCBM per week with prucalopride than with placebo. This difference was largest and significant during the first week of 4 mg prucalopride (P £ 0.05). Significantly more patients in each prucalopride group achieved an increase of ‡1 SCBM per week from baseline vs placebo (e.g. 60% with 1 mg prucalopride vs 34% with placebo at week 4; P £ 0.05). More patients had improvement in PAC-QOL satisfaction score of ‡1 with 1 mg prucalopride than with placebo (P £ 0.05); the same was true for PAC-SYM stool symptoms (1 and 4 mg prucalopride; P £ 0.05). Treatment-emergent adverse events were similar between groups: the most frequently reported with prucalopride were headache and gastrointestinal events. There were no clinically significant differences between prucalopride and placebo for vital signs, laboratory assessments, or ECG variables.
An update on prucalopride in the treatment of chronic constipation
Therapeutic advances in gastroenterology, 2017
Chronic constipation (CC) is a highly prevalent and often under-appreciated gastrointestinal disorder associated with significant impairment in quality of life. Symptoms of constipation are typically present for a number of years prior to a patient seeking help. Lifestyle modifications followed by, or coupled with, over-the-counter laxatives represent the initial treatment option; however, relief for many is limited and dissatisfaction rates for these approaches remain high. Over recent years, therefore, considerable effort has been exerted on the development of novel pharmacological approaches. Two major targets have emerged, motility and secretion. Research on the former led to the development of a number of prokinetic agents capable of stimulating colonic motility and, thus, accelerating colonic transit. Of these, earlier prototypes such as cisapride and tegaserod, though effective, were ultimately withdrawn due to cardiovascular adverse events due in part to receptor non-selecti...
Prucalopride: novel drug for chronic idiopathic constipation
International Journal of Basic & Clinical Pharmacology, 2019
Chronic Idiopathic Constipation (CIC), defined as constipation in which the underlying cause is unknown, is a common medical illness with a profound negative impact on health-related quality of life and increased propensity for life threatening complications. Current treatment for CIC includes lifestyle modifications, over-the-counter medications, and prescription medications. Presently, the only approved, prescription products for CIC in the US are prosecretory agents. However, the current knowledge that serotonin plays an important role in colonic motility has opened new horizons in the treatment of CIC promoting use of prokinetic agents with a different mechanism of action. Prucalopride is a highly selective 5-hydroxytryptamine type 4 (5-HT4) receptor agonist that enhances propulsive motor patterns in the large intestine due to a high affinity for 5-HT4 receptors in gastrointestinal (GI) tissues. The onset of action of Prucalopride is fast, shows rapid absorption, oral bioavaila...
Digestive Diseases and Sciences, 2010
Background Opioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT4 agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC. Methods A phase II, double-blind, placebo-controlled study of 196 patients randomized to placebo (n = 66), prucalopride 2 mg (n = 66) or 4 mg (n = 64), for 4 weeks, was carried out. The primary endpoint was the proportion of patients with increase from baseline of ≥1 spontaneous complete bowel movement (SCBM)/week. Secondary endpoints [proportion of patients with ≥3 SCBM/week, weekly frequency of (SC)BM, severity of constipation, and efficacy of treatment], adverse events (AEs), and safety parameters were also monitored. Results More patients had an increase from baseline of ≥1 SCBM per week (weeks 1–4) in the prucalopride groups [35.9% (2 mg) and 40.3% (4 mg)] versus placebo (23.4%), reaching statistical significance in week 1. Over weeks 1–4, more patients in the prucalopride groups achieved an average of ≥3 SBM per week versus placebo (60.7% and 69.0% versus 43.3%), reaching significance at week 1. Prucalopride 4 mg significantly improved patient-rated severity of constipation and effectiveness of treatment versus placebo. Patient Assessment of Constipation-Symptom (PAC-SYM) total scores and Patient Assessment of Constipation-Quality of Life (PAC-QOL) total and satisfaction subscale scores were improved. The most common AEs were abdominal pain and nausea. There were no clinically relevant differences between groups in vital signs, laboratory measures or electrocardiogram parameters. Conclusion In this population with OIC, prucalopride improved bowel function and was safe and well tolerated.
Neurogastroenterology and Motility, 2009
Abstract Chronic constipation is common among nursing home residents. The aim of this study was to evaluate safety, tolerability and pharmacokinetics of the selective 5HT4 receptor agonist prucalopride in elderly, chronically constipated patients in nursing homes. A multicentre, phase II, randomized, double-blind dose-escalation study in 89 elderly constipated nursing home residents treated with placebo, 0.5, 1 or 2 mg prucalopride once daily for 28 days was analysed. Adverse events, vital signs, ECG, Holter monitor and pharmacokinetics were assessed (Clinicaltrials.gov identifier: NCT00627692). Patients’ mean age was 83 years; 88% had a history of cardiovascular diseases. Most frequent adverse events, at least possibly related to prucalopride, were diarrhoea and abdominal pain. Relative to placebo, there were no differences in vital signs, ECG corrected QT interval, ECG morphology parameters, or incidence of supraventricular or ventricular arrhythmias on Holter monitoring. Plasma prucalopride concentrations increased proportionally with administered dose. Prucalopride up to 2 mg once daily for 4 weeks was safe and well-tolerated by constipated elderly patients, with no differences vs placebo in ECG or a range of Holter-monitoring parameters.
Efficacy and Safety of Prucalopride in Patients with Chronic Noncancer Pain
2013
Ó The Author(s) 2010. This article is published with open access at Springerlink.com Background Opioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT4 agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC. Methods A phase II, double-blind, placebo-controlled study of 196 patients randomized to placebo (n = 66), prucalopride 2 mg (n = 66) or 4 mg (n = 64), for 4 weeks, was carried out. The primary endpoint was the proportion of patients with increase from baseline of C1 spontaneous complete bowel movement (SCBM)/week. Secondary endpoints [proportion of patients with C3 SCBM/week, weekly frequency of (SC)BM, severity of constipation, and efficacy of treatment], adverse events (AEs), and safety parameters were also monitored. Results More patients had an increase from baseline of C1...
Journal of Digestive Endoscopy
Background Colonoscopy is currently gold standard for visualizing colonic mucosa. Presence of constipation is generally associated with poor bowel preparation. We compared effect on colonic cleansing when prucalopride was used as adjunct with polyethylene glycol (PEG) in patients of constipation. Methods A retrospective study was conducted at our center. One 70 patients with constipation were enrolled in two groups of who took only PEG and other of prucalopride plus PEG+ for bowel preparation. They underwent colonoscopy by a single-blinded experienced endoscopist. Bowel preparation quality was reported by Boston bowel preparation scale prior to washing or suctioning. The groups were analyzed for bowel preparation quality and side effects in either groups based on preformed questionnaire. Results Mean Boston Stool preparation Score (BSS) in PEG group (5.33 ± 1.43) was slightly higher than PEG+ (5.16 + 1.37) (p-value =0.44). The total number of patients with side effects was higher in...
Journal of gastroenterology and hepatology, 2017
Patients with functional bowel disorders develop gas retention and symptoms in response to intestinal gas loads that are well tolerated by healthy subjects. Stimulation of 5HT-4 receptors in the gut has both prokinetic and antinociceptive effects. To determine the effect of prucalopride, a highly selective 5HT-4 agonist, on gas transit and tolerance in women with functional bowel disorders complaining of constipation. Twenty-four women with functional bowel disorders complaining of constipation were included in the study. Patients were studied twice on separate days in a cross over design. On each study day an intestinal gas challenge test was performed. During the 5 previous days, prucalopride (2 mg/d) or placebo was administered. Abdominal symptoms, stool frequency and stool consistency were recorded during the treatment period on daily questionnaires. During the gas challenge test, prucalopride did not decrease the volume of gas retained in the subset of patients who had signific...