Turnhout, Belgium, Tuesday 10 May 2011. Shire plc (LSE: SHP, NASDAQ: SHPGY) announces that a recent additional analysis of clinical data presented at Digestive Disease Week (DDW) 2011 in Chicago, USA, reconfirm that Resolor® (prucalopride), is efficacious in women with chronic constipation in whom laxatives do not provide adequate relief.1 Once-daily prucalopride (2 mg) improves bowel function and bowel symptoms, and also improves quality of life (QoL) in patients.1Additional data presented at the congress demonstrate that colon transit times* decrease with prucalopride treatment, while the number of bowel movements increase.2
Chronic constipation is a multi-symptom disorder of persistent and prolonged nature.3 It is widespread and often severe, and is particularly prevalent in women.4 People with chronic constipation often suffer from symptoms including bloating, abdominal discomfort and infrequent bowel movements, which can have a substantial impact on a person’s QoL.3 These symptoms and other complications of chronic constipation mean that the majority of those affected report some degree of work impairment.3
Three Phase II dose-finding trials studied the relationship between bowel function and colon transit time in patients who have had chronic constipation for an average of 19 years.2These pooled data, from 280 predominantly female (92.5%) patients with a mean age of 52.5 years (18?? years), found that compared to baseline, colon transit time significantly decreased by an average of 12 hours in patients receiving 2 mg prucalopride compared with essentially no change in patients receiving placebo.2 Moreover, the decrease in colon transit time correlated with an increase in the number of bowel movements.2
“These data provide us with more information on the physiological mechanism of prucalopride,” said Dr Anton Emmanuel, Department of Gastroenterology and Nutrition, University College Hospital, London.** “Patients who take prucalopride may have shortened colon transit times; meaning that faeces move more quickly through the gut and this results in more frequent spontaneous bowel movements.”
Further data presented at the congress from pooled results of three identically designed Phase III, double-blind, placebo-controlled trials for up to 12 weeks in 458 women with chronic constipation demonstrated that the recommended adult dose of prucalopride (2 mg) was well tolerated and significantly improved bowel function, measured by the number of bowel movements per week; (p<0.001 vs. placebo) and bowel symptoms, measured by the validated Patients Assessment of Constipation Symptom questionnaire (PAC-SYM); (p<0.001 vs. placebo).1 In addition, QoL, assessed by the Patients Assessment of Constipation QoL questionnaire (PAC-QOL), improved significantly in almost 40% of the patients taking prucalopride (p<0.001 vs. placebo).1
“Patients may experience multiple and distressing symptoms of chronic constipation for many years,” said Dr Lieve Vandeplassche, Vice President Research and Development, Shire.** “These results highlight how prucalopride is an effective option for clinicians managing women whose chronic constipation is not adequately relieved with laxatives. This is also good news for patients, since prucalopride can improve their quality of life and provide relief from long-standing symptoms.”
On 3 May 2011, Shire Pharmaceuticals Ireland Ltd launched Resolor in Ireland for women with chronic constipation in whom laxatives do not provide adequate relief. The product is now reimbursable under the General Medical Services and Community Drug Schemes. Resolor is also currently available in Germany, the UK and Belgium, and will be launched in other countries in Europe in 2011 and 2012.
A new clinical trial with prucalopride in paediatric patients*** with functional constipation has been approved by the competent authorities and the Central Ethics Committee in the Netherlands. The first site initiation visit in the Netherlands took place on 26 April 2011 and the first paediatric patients have already been screened for the trial.
*Colon transit times are often too slow in patients with chronic constipation **Author of poster presented at DDW 2011
*** Resolor is not licensed for treatment in children and adolescents younger than 18 years until further data are available
For further information please contact:
Media: Ingrid Jansen (ijansen@shire.com
About Resolor® (prucalopride)5
Resolor® (prucalopride) is a selective, high-affinity 5-HT4 receptor agonist specifically developed to target impaired motility associated with chronic constipation. Resolor was approved in 30 European countries (EU27, Norway, Iceland and Liechtenstein) for the symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief in October 2009. In July 2010, Switzerland became the 31st country where prucalopride is approved for the treatment of idiopathic chronic constipation in adults for whom the currently available treatment options involving dietary measures and laxatives do not provide sufficient effect, with the statement that “there are currently no sufficient data available to evaluate the effectiveness and safety of Resolor in men”.
Resolor is a prescription-only medicine.
Dosage for women is 2 mg once daily. For elderly women over 65 years of age, starting dose is 1mg once daily and increase to 2 mg once daily if necessary. Until further data become available, prucalopride is not recommended in men, children and adolescents <18 years.
The efficacy of prucalopride was established in three multicentre, randomised, double-blind, 12-week placebo-controlled studies in subjects with chronic constipation. The primary efficacy endpoint was the proportion of subjects that reached normalisation of bowel movements defined as an average of three or more spontaneous complete bowel movements per week over the 12-week treatment period. Prucalopride 2 mg was statistically superior (p<0.001) to placebo at the primary endpoint in each of the three studies.
In all three studies, treatment with prucalopride also resulted in significant improvements in a validated and disease specific set of symptom measures, including abdominal, stool and rectal symptoms, determined at week 4 and week 12 compared with placebo. A significant benefit on a number of Quality of Life measures, such as degree of satisfaction with treatment and with bowel habits, physical and psychosocial discomfort and worries and concerns, was also observed at both the 4- and 12-week assessment time points.
Prucalopride has been shown not to cause rebound phenomena, nor to induce dependency.
The most common adverse reactions with prucalopride (seen in more than 1 patient in 10) are headache, nausea, diarrhoea and abdominal pain. The adverse reactions occur predominantly at the start of therapy and usually disappear within a few days with continued treatment. Other adverse reactions have been reported occasionally.
A thorough QT study was performed to evaluate the effects of prucalopride on the QT interval at therapeutic (2 mg) and supratherapeutic doses (10 mg) and compared with the effects of placebo and a positive control. This study did not show significant differences between prucalopride and placebo at either dose, based on mean QT measurements and outlier analysis. This confirmed the results of two placebo controlled QT studies. In double blind clinical studies, the incidence of QT-related adverse events and ventricular arrhythmias was low and comparable to placebo.
Prucalopride should not be used in patients who are hypersensitive to prucalopride or any of the excipients. It must not be used in patients with renal impairment requiring dialysis. It must also not be used in patients with intestinal perforation or obstruction, severe inflammatory conditions of the intestinal tract such as Crohn’s disease, ulcerative colitis or toxic megacolon/megarectum. Patients with severe and clinically unstable concomitant disease (e.g. liver, cardiovascular or lung disease, neurological or psychiatric disorders, cancer or AIDS and other endocrine disorders) have not been studied. Caution should be exercised when prescribing prucalopride to patients with these conditions. In particular prucalopride should be used with caution in patients with a history of arrhythmias or ischaemic cardiovascular disease. A lower dose (1 mg once daily) is recommended in patients with severe renal or severe hepatic impairment. Prucalopride is not recommended during pregnancy or breast-feeding.
To access the prucalopride Summary of Product Characteristics for full prescribing information please visit http://www.ema.europa.eu
SHIRE PLC
Shire’s strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire’s in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results.
For further information on Shire, please visit the Company’s website: www.shire.com
References
1 Tack J, Kerstens R, Vandeplassche L. Efficacy and safety of oral prucalopride in female patients with chronic constipation: pooled data of 3 pivotal trials. Poster. DDW 2011: Gastroenterol2011, in press.
2 Emmanuel A, Kerstens R, Vandeplassche L. Prucalopride improves bowel function and colonic transit time in patients with constipation. Poster. DDW 2011: Gastroenterol 2011, in press.
3 Johanson JF, Kralstein J. Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther. 2007; 25: 599-608.
4 Wald A, Scarpignato C, Mueller-Lissner S, et al. A multinational survey of prevalence and patterns of laxative use among adults with self-defined constipation. Aliment Pharmacol Ther. 2008; 28: 917-30.
5. Shire Pharmaceuticals. SPC. Summary of Product Characteristics Resolor (prucalopride), December 2010.
