# CLINICAL TRIAL FOR RENZAPRIDE(C-ers)



## SpAsMaN* (May 11, 2002)

http://www.alizyme.co.uk/news/20050421_004.htmALIZYME SUCCESSFULLY COMPLETES 'THOROUGH CARDIOVASCULAR SAFETY' CLINICAL TRIAL FOR RENZAPRIDECambridge UK, 21 April 2005: Alizyme plc (LSE:AZM) announces successful completion of its 'Thorough Cardiovascular Safety' clinical trial of renzapride, conducted under Alizyme's open Investigational New Drug (IND) in the US.The trial was a positive and placebo-controlled, four-way cross-over study, involving 44 male and female healthy volunteers; single-blinded with respect to renzapride and placebo and open-label with respect to the positive control . This study evaluated the effects of single oral therapeutic (4 mg) and supratherapeutic (20 mg) doses of renzapride, and moxifloxacin (400 mg), a drug, which at this dose is known to affect heart rhythm by prolonging the QTc interval by a small amount. Cardiac rhythm parameters were continuously monitored by ECG.Neither the 4 mg, nor the 20 mg dose, of renzapride affected the heart rhythm, using a number of approved data analysis methods. In contrast, moxifloxacin demonstrated a clear effect on heart rhythm, consistent with reported findings from other studies. Dr. Richard Palmer, Chief Executive Officer, commented:"I am delighted with the successful outcome of this trial. This critical regulatory safety study is a vitally important step forward for renzapride, as we prepare for Phase III registration trials. A 'Thorough Cardiovascular Safety' study is an increasingly essential regulatory requirement for approval of a product, particularly in the USA. The finding that there is no evidence of an effect on the heart rhythm, even at five times the anticipated therapeutic dose, emphasises the safety profile of renzapride observed to date."Dr. Joel Morganroth, Chief Scientist at eResearch Technology, Alizyme's Cardiovascular Safety Consultant commented:"Alizyme is to be congratulated on an excellent trial with clear negative results, and with no signal of any cardiac repolarization at the doses of renzapride studied."For further information, please contactr Richard Palmer, Chief Executive Officer Tim McCarthy, Finance Director ALIZYME plc Tel No: + 44 (0) 1223 896000 Lisa Baderoon/Rebecca Skye DietrichBUCHANAN COMMUNICATIONS Tel No: + 44 (0) 20 7466 5000 ------------------------------------------------Editor's NoteAlizyme plc Alizyme is a speciality biopharmaceutical development company, based in Cambridge, UK, targeting the treatment and management of gastrointestinal disorders, obesity and diabetes. It has a portfolio of products which in addition to renzapride (completed Phase IIb clinical programme for irritable bowel syndrome), includes cetilistat (completed Phase IIb in obese patients and currently in a Phase IIb trial in obese diabetic patients), COLAL-PREDÂ® (Phase III approval for the treatment of acute ulcerative colitis in Europe), and ATL-104 (currently in a Phase IIa trial for mucositis). Irritable Bowel SyndromeIBS is a common gastrointestinal disorder. Important symptoms include abdominal pain, discomfort and feelings of bloating. In IBS, the normal contractile patterns of the gut are disrupted resulting in irregular or spasmodic bowel movements. Sufferers may experience either a constipation or a diarrhoea predominant form of IBS or, in 'mixed symptom' IBS, alternate between these conditions. It has been estimated that up to 20% of adults in developed countries are affected to some degree by IBS; of these between 20-30% consult a doctor. Current treatments, which are aimed at providing symptomatic relief to IBS sufferers, include laxatives, anti-diarrhoeal and antispasmodic products. These products, however, have limited efficacy for the condition and it is generally accepted that the market is poorly served.RenzaprideAlizyme is currently investigating renzapride for the treatment of IBS. Renzapride is a potent, full 5-HT4 receptor agonist; it is also an antagonist at 5-HT3 receptors. These 5-HT receptors are believed to play a key role in controlling gastrointestinal motility and sensitivity. The unique, dual pharmacological profile of renzapride differentiates it from other drugs currently in development for the treatment of IBS. Renzapride was discovered by Beecham Research Laboratories and investigated by them initially as a gastrointestinal prokinetic agent for the treatment of gastroesophageal reflux disease. Following a collaborative agreement, Alizyme obtained full ownership of patents relating to renzapride from SmithKline Beecham prior to its merger with GlaxoWellcome.Thorough Cardiovascular Safety StudyA 'Thorough Cardiovascular Safety' study, is a study designed to closely examine the effects of a drug on the ECG (heart rhythm). The particular part of the heart rhythm of interest is called the QT interval. If a drug prolongs this interval to any great extent (after making appropriate adjustments for any change in heart rate), this may lead to serious cardiovascular safety issues in clinical use. The QT interval after adjusting for changes in heart rate is called the corrected QT (QTc). A number of formula are used for calculating the QTc. The most common are Bazett's formula (QTcB), Fridericia's formula (QTcF), and corrections for each individual subject (QTci); the latter is now regarded as the most reliable.The design of the study is that proposed by the International Conference on Harmonisation (ICH) and involves comparing the new drug at its likely clinical dose and a supratherapeutic dose (defined as 5 times the likely clinical dose), with the effects seen on placebo. As a means of checking that the study is capable of detecting an effect if one was present, a drug known to cause small prolongation of the QT interval is also included, namely moxifloxacin.eResearch TechnologyeResearch Technology, Inc. (eRT) is a provider of technology-based products and services focussing on the efficient digital collection and interpretation of cardiac safety data from clinical studies. The Company is a market leader in providing centralized, diagnostic electrocardiographic services, and a leading provider of technology and services designed to streamline the clinical trial process, by enabling its customers to automate many parts of a clinical trial.------------------------------------------------The identification of compounds for successful research, their progress through development and the obtaining of regulatory approvals or authorisations before marketing, manufacture and/or distribution of products is not certain or a formality.--------------------------------------------------------------------------------


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