Tranzyme Pharma reports positive results from Phase II gastroparesis trial

Tranzyme Pharma has reported that its 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.

Clinical trial results indicated that TZP-101 was safe and highly effective in improving multiple symptoms associated with gastroparesis, the company said. A total of 76 patients with either type 1 or type 2 diabetes mellitus and a confirmed diagnosis of gastroparesis were enrolled in a US and EU, double-blind, placebo-controlled Phase II 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-minute intravenous infusion of one of six doses of TZP-101 (20-600mcg/kg) or placebo for four 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 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 and clinician rated symptom assessment (CRSA) scores were collected for the study.

The company said that 80mcg/kg was determined to be the TZP-101 dose which achieved maximum clinical benefit. Upon completion of the four-day dosing period, improvement in symptoms in TZP-101-treated subjects was statistically significant over placebo-treated subjects as determined by one or more of the evaluation tools 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.

Vipin Garg, president and CEO of Tranzyme, said: 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 III program to further evaluate the efficacy and safety of TZP-101 in this patient population.