Dublin, Ireland, 2nd April 2008
AGI announces key findings of clinical PK study
of arbaclofen (AGI-006)
AGI Therapeutics plc ("AGI" or the "Company") (AIM,
IEX: AGI), a speciality pharmaceutical company focused on gastrointestinal
drug products, today announces the key findings of a clinical study to
assess the pharmacokinetic profile of arbaclofen (AGI-006), which is being
developed for the treatment of gastroparesis, a significant gastric condition
amongst diabetics.
The pharmacokinetic study was conducted in healthy human volunteers and compared the drug exposure profile of arbaclofen, under both fasted and fed conditions, following a single oral administration of a 5mg dose. Arbaclofen contains the purified R-isomer form of the previously approved drug baclofen (which is an equal mixture of the S- and R-isomers). In addition, this study compared the drug exposure of arbaclofen (5mg), in terms of both the S- and R-isomer forms of baclofen, with a single 10mg oral dose of Lioresal® (a marketed form of racemic baclofen).
The key findings were:
- There were no detectable S-isomer levels following arbaclofen administration and thus no evidence of any interconversion of arbaclofen (R-isomer) to S-isomer in vivo. The S-isomer is believed to partly counteract the activity of the R-isomer, the critical isomer for the beneficial effects of AGI-006 on gut function, and also contribute unwanted side effects through its own actions and effects.
- Following arbaclofen administration, approximately 80% of the administered dose was recovered in the urine in unchanged form. The high recovery of unchanged R-isomer in the urine following arbaclofen administration indicates there is no significant effect of hepatic metabolism on the kinetics of arbaclofen.
- There was comparable plasma exposure of R-isomer from 5mg of arbaclofen compared to 10 mg of Lioresal, confirming that the exposure to the R-isomer is no greater following arbaclofen administration when compared with equivalent doses of an approved and marketed form of racemic baclofen.
- The rate of drug exposure (expressed as time to peak plasma concentration, or "Tmax") and the extent of drug exposure (expressed in terms of both peak plasma concentration, or "Cmax", and area under the plasma concentration curve, or "AUC") following arbaclofen administration were only modestly reduced by food. This demonstrates that acceptable drug exposure can be achieved with AGI-006 in situations where gastric emptying is delayed (in this case food-induced), which is a key feature of the targeted gastroparesis indication.
Commenting on the results Dr John Devane said "These findings have important implications for the further clinical development of arbaclofen. We can now proceed in the knowledge that there will be no exposure to the S-isomer following administration of the purified R-isomer form contained in AGI-006. In addition, confirmation that the in vivo exposure to the R-isomer following arbaclofen administration is no greater than is seen with marketed racemic baclofen will support our 505(b)2 NDA development strategy and the associated cross-referencing of the pre-clinical and clinical safety history available on racemic baclofen."
Contact Information
AGI Therapeutics
David Kelly, Chief Financial Officer
Tel: +353 1 449 3254
Financial Dynamics - UK
Deborah Scott/Lara Mott
Tel: +44 (0) 20 7269 7182
Financial Dynamics - Ireland
Aisling Garvey
Tel: +353 1 663 3607
Piper Jaffray Limited
Neil Mackison
Will Carnwath
Tel: +44 (0) 20 3142 8700
Davy
John Frain
Tel: +353 (1) 614 8761
Notes to Editors:
About the Study
The pharmacokinetic study was a single-dose, open-label, randomized, three-way crossover study in nine healthy subjects (4 males, 5 females). The treatments were arbaclofen/AGI-006 (5mg) administered under fasting and fed conditions and Lioresal® (10mg) administered under fasting conditions. Lioresal is an FDA-approved form of racemic baclofen which is used to treat CNS disorders. Blood samples were taken periodically up to 24 hours after each administration and there was also a cumulative 24 hour collection of urine. Plasma and urine concentrations of the R- and S-isomers of baclofen were measured using a validated Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS) method. All treatments in the study were well tolerated.
About arbaclofen (AGI-006)
Arbaclofen is our product candidate for the treatment of gastroparesis and for dyspeptic conditions such as functional dyspepsia. Gastroparesis is a significant GI disorder among diabetic patients and affects up to 20% of Type I and 30% of Type II diabetics. Current drug therapy for gastroparesis is limited and there is a significant market opportunity for new safe and effective products. Arbaclofen is an oral dosage form of the predominant pharmacologically active r-isomer of baclofen.
About gastroparesis
Gastroparesis is a gastric motility disorder where there is delayed gastric emptying and the condition is usually chronic. The primary known cause of gastroparesis is diabetes and the condition is frequently referred to as 'diabetic gastroparesis'. In diabetic patients (both Types I and II), gastroparesis is caused by prolonged elevated serum glucose levels resulting in vagal nerve damage, which in turn leads to impaired gastric motility and emptying. Gastroparesis is estimated to affect up to 30% of Type I and 20% of Type II diabetics. There are an estimated 2.5 million diabetic gastroparesis patients in the US and 1.5 million in Europe, while the incidence is expected to rise as the diabetic population continues to increases across the globe.
About AGI
AGI is a speciality pharmaceutical company which is focused on the development and commercialisation of differentiated drug products for gastro-intestinal (GI) diseases and disorders. AGI's common shares are listed on the Alternative Investment Market of the London Stock Exchange (AIM) and on the Irish Enterprise Exchange of the Irish Stock Market (IEX) as AGI.
The Company has a portfolio of product candidates derived from its Known
Molecular Entity (KME) approach to drug re-profiling and development.
The Company's lead product candidate, RezularTM, is an orally administered
triple-action intestinal regulator, a first-in-class mechanism for the
treatment of diarrhoea predominant Irritable Bowel Syndrome (IBS-D).
KME is a re-profiling methodology used by the Company to identify existing
therapeutic drugs which typically have been marketed for a number of years,
have established safety profiles and can be developed for new clinical
indications or with improved profiles in their existing clinical indications.
In this way, the Company seeks to reduce the risk, time and cost of new
product development as compared to the development of new chemical entities.
AGI is developing a range of product candidates to treat a variety of prevalent GI diseases and disorders, including irritable bowel syndrome (IBS), dyspeptic symptoms, gastroparesis, ulcerative colitis, gastro-esophageal reflux disease (GERD) and diarrhoea-related conditions such as chemotherapy-induced diarrhoea (CID). The Company is targeting areas of the GI therapeutic drug products market for its product candidates where there are currently unmet medical needs or where the effectiveness of existing drug therapies can be further improved.
The Company has five active clinical stage product candidates which are either isomers or new drug delivery formulations of existing approved drugs and which have established safety and tolerability profiles in their currently approved clinical indications.
For further information please see www.agitherapeutics.com
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