Clinical trial: the efficacy of open-label prucalopride treatment in patients with chronic constipation - follow-up of patients from the pivotal studies (original) (raw)
Related papers
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...