Tranzyme Pharma Announces Positive Phase 2 Results with TZP-101 for Improvement of Symptoms in Patients with Gastroparesis
RESEARCH TRIANGLE PARK, N.C. -- Apr 22, 2009 - Tranzyme Pharma today announced that its first-in-class, potent and selective ghrelin agonist, TZP-101, demonstrated effectiveness in the treatment of gastroparesis, an inability of the stomach to empty food efficiently, especially in patients with diabetes mellitus (DM). Clinical trial results indicated that TZP-101 was safe and highly effective in improving multiple symptoms associated with gastroparesis.
A total of 76 patients with either type 1 or type 2 DM and a confirmed diagnosis of gastroparesis (by presence of both chronic symptoms and objective demonstration of delayed gastric emptying) were enrolled in a US and EU, double-blind, placebo-controlled Phase 2 trial designed to evaluate the safety and efficacy of TZP-101. Patients were voluntarily admitted to the hospital and adaptively randomized to receive a daily 30-min IV infusion of one of six doses of TZP-101 (20-600μg/kg) or placebo for 4 consecutive days. Overall, 57 subjects received TZP-101 and 19 received placebo. Patient safety was monitored by vital signs, ECGs, physical exams, clinical chemistry and adverse events.
During treatment and at a 30-day follow-up visit, efficacy was evaluated by symptom improvement as assessed by both the patients and the investigators. The Gastroparesis Cardinal Symptom Index (GCSI), a questionnaire for assessing the severity of symptoms associated with gastroparesis, was administered to each subject prior to dosing, on each of the treatment days and at the follow-up visit. Additionally, meal-related Gastroparesis Symptom Assessment (GSA) and Clinician Rated Symptom Assessment (CRSA) scores were collected for the study.
Summary Results: 80μg/kg was determined to be the TZP-101 dose which achieved maximum clinical benefit. Upon completion of the 4-day dosing period, improvement in symptoms in TZP-101-treated subjects was statistically significant (or trending toward significance) over placebo-treated subjects as determined by one or more of the evaluation tools (GCSI, GSA, CRSA) for the following symptoms: vomiting (p=0.006), loss of appetite (p=0.034), postprandial fullness (p=0.007), early satiety (p=0.087), abdominal distension (p=0.053) and bloating (p=0.0822). Statistical significance was also observed by the CRSA Overall Symptom scores (p=0.046). The 30-day follow-up evaluation demonstrated a sustained benefit in symptom improvement in the TZP-101 group. This effect reached statistical significance (p=0.023) for vomiting, a particularly debilitating complication of gastroparesis. In addition, proportionally fewer subjects (3%) in the TZP-101 group required hospitalization for gastroparesis during the 30-day follow-up period versus the placebo group (10%). TZP-101 was safe and well-tolerated at all doses tested.
"We are encouraged to see that TZP-101, given intravenously for only 4 days, induced an acute and sustained reduction of symptoms offering a potential new therapy for patients with gastroparesis and other GI motility disorders in acute settings," said Gordana Kosutic, MD, Vice President, Clinical and Regulatory Affairs for Tranzyme. "These results are consistent with the potent prokinetic properties of TZP-101 and complement our previously reported successful Phase 2 study with TZP-101 for the management of postoperative ileus (POI)."
"We recognize the severity of symptoms caused by gastroparesis and their impact on quality of life, and are anxious to bring relief to the millions of patients suffering from this condition. We now plan to initiate a Phase 3 program to further evaluate the efficacy and safety of TZP-101 in this patient population," stated Vipin K. Garg, PhD, President and CEO of Tranzyme.
About Gastroparesis
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 postprandial 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 are impaired. Gastroparesis may also result from abdominal surgery or be idiopathic in nature. Current medications for the treatment of gastroparesis are limited, are only moderately efficacious and have undesirable side effects (most notably, neurological effects). It is estimated that approximately 5 million patients suffer from gastroparesis in the US.
About TZP-101
TZP-101, Tranzyme's intravenous ghrelin agonist, is the first product from the Company's internal drug discovery efforts. TZP-101 is in clinical development for the treatment of POI and gastroparesis in acute care settings and has the potential to treat other conditions requiring administration of intravenous prokinetic agents. The safety and pharmacokinetic profiles of TZP-101 have been extensively characterized in healthy subjects and patients across multiple dose levels, and the GI prokinetic properties of the compound have been well established in various animal models and humans. In addition to TZP-101, Tranzyme is also developing an oral ghrelin agonist, TZP-102, for the out-patient treatment of gastroparesis and other chronic GI and motility disorders, including GERD, functional dyspepsia, OBD and IBS-C.
About Tranzyme Pharma
Tranzyme Pharma is a late stage biopharmaceutical company engaged in the discovery and development of first-in-class small molecule therapeutics for the treatment of both acute care (hospital-based) and chronic indications with significant unmet medical needs. For more information on Tranzyme, please visit: www.tranzyme.com.