Glenmark Pharmaceuticals' lead DPP-IV inhibitor candidate for diabetes, GRC 8200, has successfully completed its phase I study. The study was filed with the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK and was conducted by Parexel UK, a leading global CRO.

The objective of the phase I study was to assess the safety and bioavailability of GRC 8200 in humans and was conducted using single and multiple oral doses on 88 healthy volunteers. It was found that the compound was very well tolerated by the subjects at all dosage levels and there were no significant adverse events reported. The study design included eight single dose regimens with 800mg as the highest dose, states the company release.

The pharmacokinetic profile of GRC 8200 was linear across the dosage range studied and was found to be favourable to support a once-daily regimen. More than 90% inhibition of the DPP-IV enzyme was observed within an hour at all doses tested. The study also included three multiple dose (10 days) regimens with 300mg/day as the highest dose.

GRC 8200 has now entered phase II testing with trials that are beginning in South Africa at a US FDA approved CRO. The company also intends to file a US IND for GRC 8200 by May 2006 for further phase II clinical testing and expects to complete all phase II trials by March 2007.

Glenn Saldanha, managing director and CEO of Glenmark Pharmaceuticals Ltd., stated, "There are several leading multinational companies who have lead molecules for DPP-IV inhibitors in early to late stage clinical trials. But with our aggressive timeline we hope to be the fourth to market with GRC 8200 in the DPP-IV class. We maintain our guidance for launching GRC 8200 in the US market in 2010."

Pre-clinical studies demonstrated GRC 8200 to be many times more potent (I.C. 50=1.61nM) than competing DPP-IV inhibitors. The compound is highly bio-available (50%-95% oral bioavailability across species) and safe, displaying significant reduction in glucose excursion on oral glucose challenge (50%-75% across species). Pre-clinical studies also demonstrated that GRC 8200 has the potential of being a long-acting compound with high selectivity to the DPP-IV target over DPP-II, VIII and IX.

In line with its policy of partnering its NCEs with strong development and marketing partners for North America, Europe and Japan, Glenmark is in early discussions with potential partners in the regulated markets to collaborate on the clinical development, filing and marketing of this product.