Market Wire - AGI Therapeutics plc announces key findings of clinical PK study of arbaclofen (AGI-006)
AGI announces key findings of clinical PK study of arbaclofen (AGI-006)
Dublin, Ireland, 2 April 2008 - 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:
(1) 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.
(2) 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.
(3) 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.
(4) 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 plc. Tel: 353 1 449 3254
David Kelly, Chief Financial Officer
Financial Dynamics - UK Tel: 44 (0) 20 7269 7182
Deborah Scott/Lara Mott
Financial Dynamics - Ireland Tel: 353 1 663 3607
Aisling Garvey
Piper Jaffray Limited Tel: 44 (0) 20 3142 8700
Neil Mackison
Will Carnwath
Davy Tel: 353 1 614 8761
John Frain
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.
