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Shire Pharmaceuticals Group Plc

Shire Receives European Approval to Use Resolor® (prucalopride) in Men for the Symptomatic Treatment of Chronic Constipation

Switzerland (ots/PRNewswire)

For Release in Europe Only

- Resolor was approved in 2009 in Europe for use in women for the
  symptomatic treatment of chronic constipation in whom laxatives fail to provide
  adequate relief[1]

Shire plc announced today that Resolor (prucalopride) has been approved by the European Medicines Agency for use in adults for the symptomatic treatment of chronic constipation in whom laxatives fail to provide adequate relief. Resolor is approved for use in women in Europe, so the new variation extends the use of this treatment to male patients.[1]

Chronic constipation is characterised by infrequent and difficult passage of stools over a prolonged period, and includes a range of symptoms.[2] It is estimated to affect up to 14% of the population, with an incidence rate of 17% in women and 9% in men.[3] It is often a persistent condition that can impact significantly on a patient's quality of life.[2] Resolor is a selective, high-affinity 5-HT4 receptor agonist, which helps to stimulate bowel motility.[1],[4]-[7]

"Constipation can cause severe symptoms, affect quality of life and lead to significant healthcare resource utilisation," commented Professor Yan Yiannakou, Principal trial investigator of the Resolor male study and Professor of Neurogastroenterology, Durham, UK. "We know that laxatives are often inadequate or unsatisfactory for patients with chronic constipation. The availability of prucalopride for men now offers an effective treatment option when laxatives fail to provide symptom relief."

The efficacy, safety and tolerability of Resolor in male patients with chronic constipation were evaluated in a 12-week, multicentre, randomised, double-blind, placebo-controlled study (N=370). The data showed that a statistically significantly higher percentage of subjects in the Resolor group (37.9%) experienced normal bowel function, as assessed by an average of greater than or equal to3 spontaneous complete bowel movements (SCBMs) per week, compared with subjects in the placebo treatment group (17.7%) (p<0.0001) over the 12-week treatment period. The most common adverse events associated with Resolor were headache and gastrointestinal disorders. The safety profile of Resolor was consistent with that seen in studies of female patients.[1],[8]

"The extension of the Resolor label to include use in men is an important development in the treatment of chronic constipation," said Roger Adsett, Head of the Gastrointestinal and Internal Medicines Business Unit at Shire. "We are pleased to now be able to offer the benefits of Resolor to even more chronic constipation patients in need of treatment options."

Resolor was first approved in Europe in 2009 for the symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief.[1]

About Resolor (prucalopride)

Resolor is a selective, high-affinity 5-HT4 receptor agonist with gastrointestinal prokinetic effects.[1] Resolor binds to and stimulates 5-HT4 receptors, which are involved in the stimulation of high-amplitude propagated contractions (HAPCs) and co-ordination of bowel motility.[4]-[7] In an integrated analysis of six large randomised controlled clinical trials including males and females, it was shown that more than 1 in 4 adult patients experienced normal bowel function (average of greater than or equal to3 SCBMs per week over 12 weeks) with Resolor. This was more than twice that of placebo.[1],[9],[10]

Resolor is indicated in European Union (EU), Iceland, Liechtenstein and Norway for the symptomatic treatment of chronic constipation in adults in whom laxatives fail to provide adequate relief.[1]

Resolor Important Safety Information[1]

In controlled clinical trials, very common adverse reactions (frequency greater than or equal to1/10) with Resolor 2mg therapy were headache, nausea, diarrhoea and abdominal pain. Common adverse reactions (greater than or equal to1/100 to <1/10) were decreased appetite, dizziness, vomiting, dyspepsia, flatulence, abnormal gastrointestinal sounds, and fatigue.

Contraindications

Hypersensitivity to the active substance or to any of the excipients; renal impairment requiring dialysis; intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract, such as Crohn's disease, and ulcerative colitis and toxic megacolon/megarectum.

Special warnings and precautions for use

Severe diarrhoea, severe renal impairment, severe hepatic impairment, severe and clinically unstable concomitant disease (e.g. cardiovascular or lung disease, neurological or psychiatric disorders, cancer or AIDS and other endocrine disorders), history of arrhythmias or ischaemic cardiovascular disease; galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

Please consult the Resolor Summary Product Characteristics (SmPC) for full safety information.

About chronic constipation

Patients with chronic constipation experience multiple symptoms such as hard stools, straining, abdominal discomfort, infrequent bowel movements, bloating, gas, feeling of incomplete evacuation after a bowel movement, abdominal pain, rectal pain and sudden urge to have a bowel movement.[2] Constipation can be caused by impaired coordination of bowel motility. In patients with chronic constipation, the frequency and duration of HAPCs are reduced in comparison with healthy individuals.[11]-[13]

NOTES TO EDITORS

Shire enables people with life-altering conditions to lead better lives.

Our strategy is to focus on developing and marketing innovative specialty medicines to meet significant unmet patient needs.

We focus on providing treatments in Rare Diseases, Neuroscience, Gastrointestinal, and Internal Medicine and we are developing treatments for symptomatic conditions treated by specialist physicians in other targeted therapeutic areas, such as Ophthalmics.

http://www.shire.com

References

1) Resolor(R) (prucalopride), EMA Summary of Product Characteristics. Shire
  Pharmaceuticals Ireland Limited, May 2015.
2) Johanson JF, Kralstein J. Chronic constipation: a survey of the patient
  perspective. Aliment Pharmacol Ther 2007;25:599-608.
3) Suares NC, Ford AC. Prevalence of, and risk factors for chronic idiopathic
  constipation in the community: Systematic Review and Meta-analysis. Am J Gastroenterol
  2011;106:1582-91.
4) Briejer MR, Prins NH, Schuurkes JA. Effects of the enterokinetic prucalopride
  (R093877) on colonic motility in fasted dogs. Neurogastroenterol Motil 2001;13:465-72.
5) Gershon MD, Tack J. The serotonin signaling system: from basic understanding
  to drug development for functional GI disorders. Gastroenterology 2007;132:397-414.
6) De Schryver AMP, Andriesse GI, Samsom M, et al. The effect of the specific
  5HT4 receptor agonist, prucalopride, on colonic motility in healthy volunteers.
  Aliment Pharmacol Ther 2002;16:603-12.
7) Manabe N, Wong BS, Camilleri M. New-generation 5-HT4 receptor agonists:
  potential for treatment of gastrointestinal motility disorders. Expert Opin Investig
  Drugs 2010;19:765-75.
8) Yiannakou Y, Piessevaux H, Bouchoucha M, et al. A randomized, double-blind,
  placebo-controlled phase 3 trial to evaluate the efficacy, safety and tolerability of
  prucalopride in men with chronic constipation. Am J Gastroenterol 2015;110:741-8.
9) Camilleri M, Kerstens R, Rykx A, et al. A placebo-controlled trial of
  prucalopride for severe chronic constipation. N Engl J Med 2008;358:2344-54.
  10) Piessevaux H, Camilleri M, Yiannakou Y et al. Efficacy and safety of
  prucalopride in chronic constipation:an integrated analysis of six randomized
  controlled clinical trials. Gastroenterology 2015;148:S-311.
  11) Bassotti G, Chistolini F, Marinozzi G, et al. Abnormal colonic propagated
  activity in patients with slow transit constipation and constipation-predominant
  irritable bowel syndrome. Digestion 2003;68:178-83.
  12) Bassotti G, Chiaroni G, Vantini I, et al. Anorectal manometric abnormalities
  and colonic propulsive impairment in patients with severe chronic idiopathic
  constipation. Dig Dis Sci 1994;39:1558-64.
  13) Camilleri M, Ford MJ. Review article: colonic sensorimotor physiology in
  health, and its alteration in constipation and diarrhoeal disorders. Aliment Pharmacol
  Ther 1998;12:287-302.
For further information please contact:
Investor Relations
Sarah Elton-Farr 
seltonfarr@shire.com
+44(0)1256-894157

Media
Lauren O'Brien 
lobrien@shire.com
+41-44-288-4040

Weitere Storys: Shire Pharmaceuticals Group Plc
Weitere Storys: Shire Pharmaceuticals Group Plc