June 23, 2008
Tranzyme Pharma Announces Successful Thorough QT/QTc Study of Ghrelin Agonist TZP-101
Tranzyme Pharma announces the successful results from a "Thorough QT/QTc" study of the company's lead product TZP-101, an intravenous gastrointestinal prokinetic agent currently in two Phase IIb trials for the treatment of postoperative ileus (POI) and severe gastroparesis.
The study, required by the US Food and Drug Administration (FDA) for all new chemical entities, was conducted to evaluate the cardiac safety of TZP-101, with a focus on cardiac repolarization as measured by the duration of the QT interval in serial electrocardiograms (ECG). TZP-101 has a novel mechanism of acting as an agonist of the body's ghrelin receptors, whereas other known gastrointestinal (GI) prokinetics act on serotonin receptors and have been linked to life-threatening cardiac side effects related to QT interval prolongation resulting in their restriction or removal from the market.
The trial was a double-blind, randomized, parallel study which compared the ECG effects of TZP-101, given at a therapeutic (160ug/kg daily for 5 days) and a supratherapeutic dose (600ug/kg daily for 5 days), to placebo and moxifloxacin (a positive control known to increase the QT interval) in 160 healthy men and women. The primary analysis was centered on a time-matched change from baseline in corrected QT interval (QTc) based on an individual correction method.
"The extensive data, including a careful pharmacokinetic-pharmacodynamic analysis, from this validated trial, clearly show that TZP-101 does not affect cardiac repolarization," stated Gordana Kosutic, MD, Tranzyme's VP, Clinical and Regulatory Affairs. "The results further demonstrate that TZP-101 has no effect on heart rate, PR and QRS interval duration or cardiac morphology, and thus continues to substantiate the compound's pronounced cardiovascular safety profile," she added.
TZP-101 is an intravenous ghrelin agonist that Tranzyme is evaluating in two concurrent Phase IIb trials for the treatment of postoperative ileus (POI) and severe gastroparesis. The safety and pharmacokinetic profile of TZP-101 has been extensively characterized in healthy subjects across multiple dose levels, and the prokinetic properties of the compound have been well established in various animal models and a preliminary investigation in diabetic patients. In addition to TZP-101, Tranzyme is developing an oral ghrelin agonist, TZP-102, currently in Phase I trials for the treatment of mild-to-moderate gastroparesis and other chronic GI motility disorders.
About Postoperative Ileus
Postoperative ileus is a transient impairment of GI motility following abdominal or other surgery. Common symptoms include abdominal distention or bloating, pain, nausea and vomiting, and inability to pass stools and tolerate a solid diet. A delay in resuming a normal diet may lead to poor healing through a cascade of events. A greater risk for pulmonary complications also exists, since POI may result in reduced patient mobility. POI is associated with an increased length of hospital stay and is the most common cause of delayed hospital discharge after abdominal surgery. In the United States alone, it is estimated that 22 million patients undergo surgical procedures requiring pain management and of these patients, 2.4 million undergo high risk open surgery each year (Source: Premier Database). No unrestricted treatments for POI have been approved by the US Food and Drug Administration to date.
Gastroparesis is an impairment or paralysis of upper gastrointestinal tract function characterized by delayed gastric emptying in the absence of mechanical obstruction. Symptoms of gastroparesis include post-prandial fullness, early satiety, abdominal pain, nausea, vomiting and weight loss. Disease severity ranges from mild to severe. Gastroparesis is a major complication of diabetes leading to metabolic imbalance when liquid and food intake and absorption of oral medications is impaired. Gastroparesis may also result from abdominal surgery or be idiopathic in nature. Current medications for the treatment of gastroparesis are only moderately effective and many are associated with adverse neurological side effects. It is estimated that approximately 5 million patients suffer from gastroparesis in the United States.
About Tranzyme Pharma
Tranzyme Pharma is a clinical stage biopharmaceutical company focused on discovering and developing first-in-class therapeutics for the treatment of both acute (hospital-based) and chronic gastrointestinal and metabolic disorders with significant unmet medical needs. For more information, please visit: www.tranzyme.com.