Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: a randomized, placebo-controlled study

Background Gastroparesis, a chronic disorder of abnormal gastric motility, is common in patients with diabetes mellitus. A synthetic, selective ghrelin receptor agonist, TZP-101, is in clinical development for treatment of gastroparesis. This double-blind, randomized, placebo-controlled study evaluated the safety and efficacy of multiple TZP-101 doses in patients with moderate to severe symptomatic diabetic gastroparesis. Methods Patients were admitted to the hospital and adaptively randomized to receive a single 30-min intravenous infusion of 20, 40, 80, 160, 320, or 600 mu g kg-1 TZP-101, (n = 57) or placebo, (n = 19) for four consecutive days. Symptoms were evaluated daily with the patient-rated Gastroparesis Cardinal Symptom Index (GCSI) and Gastroparesis Symptom Assessment (GSA). Clinicians rated gastroparesis symptoms on treatment day 4. Key Results The 80 mu g kg-1 dose was identified as the most effective dose. On day 4, there was statistically significant improvement compared with placebo in the severity of GCSI Loss of Appetite and Vomiting scores for that dose group (P = 0.034 and P = 0.006). In addition, at the 80 mu g kg-1 dose, the proportion of patients with at least 50% improvement in vomiting score was significantly different (P = 0.019) compared with placebo. Meal-related GSA scores for Postprandial fullness were significantly improved in the 80 mu g kg-1 TZP-101 group compared with placebo (P = 0.012). Clinicians rated the 80 mu g kg-1 group better improved than placebo for overall symptom assessment (P = 0.047). Safety profiles were similar in the placebo and TZP-101 groups and all doses were well-tolerated. Conclusions & Inferences TZP-101 appears to be safe, well-tolerated, and effective at acutely addressing several gastroparesis symptoms.