Using scintigraphy and a standardized meal, this double blind, randomized, four-way crossover study assessed the efficacy of three different dose levels of TZP-101 on gastric emptying in patients with long standing Type 1 diabetes and severe gastroparesis. The data showed that TZP-101 significantly accelerated gastric emptying at all doses tested, whereas placebo had no effect. These results suggest that TZP-101 is a promising agent for the management of gastroparesis and that further investigation is warranted.
"These data are very encouraging and I am looking forward to continuing with the clinical investigation of TZP-101 in patients with severe diabetic gastroparesis, as ghrelin is one of the most attractive targets for the therapeutic management of this serious medical condition," said Dr. Niels Ejskjaer, principal investigator from the Aarhus University Hospital, Denmark.
Gastroparesis is a disorder characterized by delayed emptying of food from the stomach. It exists in mild to moderate (chronic) and severe (acute) forms and is a common disorder among diabetics, and others with impaired gastric autonomic nerve function. In severe cases, patients may require hospitalizat ion to treat pain, nausea, vomiting, and even malnutrition. Gastroparesis represents a significant unmet medical need as Propulsid(TM) (cisapride), the most widely used product for treating this disorder was removed from the U.S. market in 2000 due to significant cardiovascular adverse effects.
Tranzyme earlier reported that TZP-101 demonstrated excellent tolerability and safety, as well as a desirable pharmacokinetic profile in healthy subjects in two Phase I clinical studies. The Company plans to initiate full Phase II development of TZP-101 for both POI and severe gastroparesis in 3Q 2007. In addition to the ongoing clinical testing of TZP-101 (an intravenous drug), Tranzyme is developing a new oral ghrelin agonist, TZP-102. Tranzyme expects to initiate Phase I clinical testing of TZP-102 in the first quarter of 2008 for the treatment of mild to moderate chronic gastroparesis.
"The Company is making great progress in the development of TZP-101," said Dr. Vipin Garg, President & CEO of Tranzyme Pharma. "Tranzyme's novel ghrelin agonists (TZP-101 and TZP-102) are promising breakthrough drugs with huge commercial potential. Most prokinetic agents under development and on the market act on predominantly central nervous system receptor targets that are also found in the GI tract. Many show potentially serious CNS side effects. Our small molecule ghrelin agonists target a receptor that is more directly involved with regulating gastrointestinal motility."
Gastroparesis results from dysfunction of the nerves of the stomach, leading to postprandial fullness, bloating, early satiety, nausea and vomiting. The three most common etiologies of gastroparesis are diabetes (an estimated 30% of gastroparesis patients), unknown etiology (36%), and post-surgical causes (13%). The prevalence rate of gastroparesis is especially high among diabetic patients, as up to 50% of diabetics worldwide are reported to suffer from gastroparesis . Gastroparesis has serious implications in diabetic patients, where failure to tolerate food and oral medications may lead rapidly to metabolic instability and the need for immediate treatment or hospitalization. Alternative therapeutic approaches, applicable in limited cases, include surgery, botulinum toxin injections (to reduce pyloric tone) and electrical stimulation of the gut.
Tranzyme Pharma discovers and develops breakthrough small molecule drugs for diseases where there is a high unmet medical need. Tranzyme has developed a pipeline of novel drugs for the treatment of gastrointestinal and metabolic diseases. Tranzyme's proprietary chemistry technology and discovery capabilities provide competitive advantages in developing drugs being sought by pharmaceutical companies. For more information, please visit: www.tranzyme.com.
Vipin K. Garg, Ph.D., President & CEO, 919-313-4764
Mark L. Peterson, Ph.D.
VP, Operations & Intellectual Property
Gordana Kosutic, M.D.
VP, Clinical & Regulatory Affairs