New Published Data Support Safety and Efficacy of RESOLOR(R) for Treatment of Chronic Constipation
Turnhout, Belgium (ots/PRNewswire) -
- New Generation Compound Provides Significant Benefit in Patients who do not Adequately Respond to Laxatives
New phase III data for RESOLOR(R) (prucalopride) published today in The New England Journal of Medicine (NEJM) shows statistically and clinically significant improvement of bowel function and reduced severity of symptoms in patients with chronic constipation(1). Prucalopride is the most advanced in a new generation of selective, high-affinity 5-HT4 receptor agonists, specifically designed to help patients for whom laxatives do not provide adequate relief.
In this randomized, placebo-controlled trial of 620 patients with severe chronic constipation, the proportion of patients achieving the primary study endpoint of average greater than or equal to 3 spontaneous complete bowel movements per week (SCBM/week) was significantly higher in both Prucalopride groups (2mg and 4mg) compared with placebo over both 4 and 12 weeks of treatment. Additionally, Prucalopride significantly improved the secondary efficacy endpoints, including satisfaction with bowel function and treatment, abdominal and stool symptoms, perception of constipation severity, and disease-related quality of life.
Jan Tack, Professor and Head of Clinic, Division of Gastroenterology, University Hospital Gasthuisberg, University of Leuven, Belgium, commented, "These are valuable and relevant findings because the demanding endpoint in this study combines both a subjective measure of the completeness of evacuation with an objective measure of the number of bowel movements, reflecting relief of chronic constipation and normalization of bowel function. The high selectivity of Prucalopride towards the 5-HT4 receptor offers the benefit that patients are unlikely to suffer from the side effects associated with the older generation, nonselective compounds. This meets the needs of doctors and patients by offering an effective treatment with an improved side effect profile."
Dirk Reyn, CEO of Movetis, added, "We are pleased with the publication of this data in NEJM because it gives credibility and support to the strength of our phase III dataset. It also reflects the need for a safe, efficacious treatment of chronic constipation which is currently unmet. For years, the impact of chronic constipation has been underestimated and research relating to this condition has been much less than in other medical fields. In Europe alone, approximately 10 million patients visit their doctors seeking help after unsatisfactory results with over-the-counter medications. We hope that RESOLOR(R) will help to improve the lives of these patients both in Europe and worldwide."
About the trial
The phase III trial, the second of three identical, multi-centre, parallel-group, randomized, double-blind, placebo-controlled trials, evaluated 620 adult patients with a history of chronic constipation (defined as less than or equal to 2 SCBM/ week for a minimum of 6 months prior to the selection visit). In addition, patients had to experience very hard or hard stools, a sensation of incomplete evacuation, or straining during defecation with at least 25% of their bowel movements. The primary objective was to assess the proportion of patients reporting on average three or more SCBM/week during a 12 week treatment period - a very demanding primary endpoint.
Patients received oral doses of 2mg or 4mg Prucalopride, once daily, for 12 weeks. Percentages of patients with greater than or equal to 3 SCBM/week averaged over 12 weeks respectively were:
- 12.0% for placebo
- 30.9% for 2mg Prucalopride
- 28.4% for 4mg Prucalopride.
The following secondary endpoints were significantly improved with 2mg and 4mg Prucalopride over 12 weeks:
- Percent of patients with an average increase of greater than or equal to 1 SCBM/week (p<0.001)
- Average number of spontaneous complete bowel movements per week (p<0.001)
- Percentage of bowel movements with normal consistency (p<0.001)
- Patients rating treatment effective or extremely effective (p<0.001)
- Stool and abdominal symptom scores (p<0.001)
- Percent of patients with an improvement of greater than or equal to 1 point on a disease specific and validated Quality of Life scale (PAC-QOL) (p<0.001)
Prucalopride (2mg and 4mg) also significantly reduced time to first spontaneous complete bowel movements and reduced laxative use during treatment compared to placebo (both p<0.001)
Prucalopride was well tolerated in this study population. The most frequent Adverse Events were headache, nausea and diarrhea. There were no significant cardiovascular effects of treatment. There were no differences between treatment groups in lab values, vital signs or ECG parameters.
RESOLOR (prucalopride ) is a novel enterokinetic treatment for chronic constipation in a patient population not adequately relieved by laxative treatments. It is a selective, high-affinity 5-HT4 receptor agonist, which increases colon motility and restores the slow movement of the bowels in a dose-dependent manner. RESOLOR has completed three Phase III studies and has been tested in more than 3,000 patients. Movetis filed for European marketing approval in April 2008.
About chronic constipation
Chronic constipation is a disorder of the gastrointestinal tract. It is a prevalent and debilitating condition that is not always well understood and in many cases inadequately treated. The ROME III guidelines define chronic constipation as two or more of the following symptoms at least a quarter of the time for at least six months: straining, lumpy or hard stools, a sensation of incomplete evacuation, a sensation of anorectal obstruction or blockage, and/or less than 3 defecations per week(2) . In Europe, an estimated 10 million patients frequently visit their doctors with complaints of constipation after dissatisfactory results with over-the-counter medication(3). Constipation is more common in women than men (estimated prevalence ratio of 2.2:1)(4).
Through a clear focus on gastroenterology, Movetis seeks to improve the lives of millions of patients - both adults and children - by discovering, developing and ultimately commercializing innovative treatments targeting GI conditions with a high unmet medical need. Movetis NV - founded in Belgium in December 2006 - aims to become a leading European specialty pharmaceutical organization focused on GI diseases. Movetis has a broad GI portfolio with four products in clinical development and four in preclinical, all addressing important GI areas with fewer innovative products, including chronic constipation, ascites, paediatric reflux in infants, diabetic gastroparesis and non erosive reflux disease. In addition, Movetis owns a large library of qualified lead compounds with potential for development in disease areas such as secretory diarrhea. The current portfolio has been licensed from Janssen Pharmaceutica NV, Belgium and Ortho-McNeil Pharmaceutical Inc., two Johnson & Johnson (J&J) companies.
The current portfolio includes:
- RESOLOR (prucalopride), a compound for the treatment of chronic constipation currently filed for review for Marketing Authorisation in Europe
- M0002, a selective V2 receptor antagonist compound for the treatment of ascites that has concluded recruitment of a Phase IIa trial. Results are expected before the end of Q2 2008.
- M0003, a gastrokinetic compound for the treatment of paediatric reflux in infants and symptoms of gastroparesis, which has entered a Phase IIa clinical trial in Q1 2008.
- M0004, another gastrokinetic compound for motility complaints related to non erosive or refractory gastro-oesophageal reflux disease (GORD) ready to move into clinical development.
1. Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A Placebo-Controlled Trial of Prucalopride for Severe Chronic Constipation. NEJM 2008 In Press
2. A Drossman (2006) Rome III: The new criteria. Chinese Journal of Digestive Diseases 7 (4) , 181-185.
3. IMS Health.
4. Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol 2004;99:750-9.
ots Originaltext: Movetis NV
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